Sains Malaysiana 52(3)(2023): 1273-1289

http://doi.org/10.17576/jsm-2023-5203-18

 

Emerging Role of SMYD Family of Proteins in Human Tumorigenesis

(Kemunculan Peranan Famili SMYD Protein dalam Tumorigenesis Manusia)

 

AFSHAN BIBI, AYESHA SARFRAZ, AMNA SAJJAD*, IQRA SARFRAZ, AASMA MUNAWWAR, ANEEQA ZARBAB, MEHRAN SATTAR & AZHAR RASUL

 

Department of Zoology, Faculty of Life Sciences, Government College University, Faisalabad, 38000 Pakistan

 

Received: 4 April 2022/Accepted: 7 February 2023

 

Theses authors contributed equally to this work

 

Abstract

Protein lysine methylation is a post-translational modification (PTM) that promotes protein complex formation to regulate DNA replication, gene expression, and repair mechanisms. The Su(Var)3–9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND) domain-containing proteins SMYD are lysine methyltransferases that catalyze the methylation of various histone and non-histone proteins. There are five members of this SMYD family, and all of these have conserved SET and MYND domains. The SET domain is divided into two segments by the MYND domain (the S-sequence and a core SET domain). SMYD Family performs a key role in numerous biological functions, including growth, development, apoptosis, and proliferation. SMYD family members are associated with skeletal and cardiac muscle physiology and pathology. Several studies have shown that aberrant lysine methylation plays a significant role in oncogenesis. Recently, the SMYD family has gained importance for its role in various mechanisms involved in cancer development and progressions, such as methylation and modification of tumor suppressor proteins (p53 and pRb), transcriptional factors (STAT3, NF-κB), nuclear proteins (PARP1), chaperons (Hsp90), protein kinases (MAPK, ERK), and cell cycle regulatory proteins (CDKN2). SMYD family proteins drive oncogenesis, lead the way to metastasis, and develop chemoresistance, allowing cancer cells to grow, invade the neighboring tissues, and resist therapeutics. In this review, we summarize SMYD family members' role in different cancers by focusing on their histone and non-histone methylation targets and illustrating the mechanism of SMYD family-mediated oncogenesis

 

Keywords: Cancer; chemoresistance; oncogenesis; SMYD family; tumor suppressor proteins

 

Abstrak

Pemetilan protein lisin ialah pengubahsuaian pasca translasi (PTM) yang menggalakkan pembentukan kompleks protein untuk mengawal selia replikasi DNA, pengekspresan gen dan mekanisme pembaikan. Protein yang mengandungi domain Su(Var)3–9, Enhancer-of-zeste dan Trithorax (SET) dan Myeloid, Nervy dan DEAF-1 (MYND) ialah lisin metiltransferase yang memangkinkan pemetilan pelbagai protein histon dan bukan histon. Terdapat lima ahli famili SMYD ini dan kesemua mereka telah memulihara domain SET dan MYND. Domain SET dibahagikan kepada dua segmen oleh domain MYND (jujukan S dan domain SET teras). Famili SMYD melaksanakan peranan penting dalam pelbagai fungsi biologi, termasuk pertumbuhan, perkembangan, apoptosis dan percambahan. Ahli famili SMYD dikaitkan dengan fisiologi dan patologi otot rangka dan jantung. Beberapa kajian telah menunjukkan bahawa pemetilan lisin yang menyimpang memainkan peranan penting dalam onkogenesis. Baru-baru ini, famili SMYD telah mendapat kepentingan untuk peranannya dalam pelbagai mekanisme yang terlibat dalam perkembangan dan janjangan kanser, seperti pemetilan dan pengubahsuaian protein penindas tumor (p53 dan pRb), faktor transkrip (STAT3, NF-κB), protein nuklear (PARP1)), chaperon (Hsp90), kinase protein (MAPK, ERK) dan protein pengawalseliaan kitaran sel (CDKN2). Protein famili SMYD memacu onkogenesis, membawa kepada metastasis dan membangunkan rintangan kimia, membolehkan sel kanser berkembang, menyerang tisu jiran dan menentang terapeutik. Dalam ulasan ini, kami meringkaskan peranan ahli famili SMYD dalam kanser yang berbeza dengan memfokuskan pada sasaran pemetilan histon dan bukan histon dan menggambarkan mekanisme onkogenesis pengantara famili SMYD.

 

Kata kunci: Famili SMYD; kanser; kemoterapi; onkogenesis; protein penindas tumor

 

REFERENCES

Abu-Farha, M., Lanouette, S., Elisma, F., Tremblay, V., Butson, J., Figeys, D. & Couture, J.F. 2011. Proteomic analyses of the SMYD family interactomes identify HSP90 as a novel target for SMYD2. J. Mol. Cell Biol. 3(5): 301-308. doi: 10.1093/jmcb/mjr025

Abu-Farha, M., Lambert, J.P., Al-Madhoun, A.S., Elisma, F., Skerjanc, I.S. & Figeys, D. 2008. The tale of two domains: Proteomics and genomics analysis of SMYD2, a new histone methyltransferase. Mol. Cell. Proteomics 7(3): 560-572. doi: 10.1074/mcp.M700271-MCP200

Ahmed, H., Duan, S., Arrowsmith, C.H., Barsyte-Lovejoy, D. & Schapira, M. 2016. An integrative proteomic approach identifies novel cellular SMYD2 substrates. J. Proteome Res. 15(6): 2052-2059. doi: 10.1021/acs.jproteome.6b00220

Al-Shar'i, N.A. & Alnabulsi, S.M. 2016. Explaining the autoinhibition of the SMYD enzyme family: A theoretical study. J. Mol. Graph Model 68: 147-157. doi: 10.1016/j.jmgm.2016.07.001

Allan, R.K. & Ratajczak, T. 2011. Versatile TPR domains accommodate different modes of target protein recognition and function. Cell Stress Chaperones 16(4): 353-367. doi: 10.1007/s12192-010-0248-0

Allfrey, V.G. & Mirsky, A.E. 1964. Structural modifications of histones and their possible role in the regulation of RNA synthesis. Science 144(3618): 559. doi: 10.1126/science.144.3618.559

Alshiraihi, I.M., Jarrell, D.K., Arhouma, Z., Hassell, K.N., Montgomery, J., Padilla, A., Ibrahim, H.M., Crans, D.C., Kato, T.A. & Brown, M.A. 2020. In Silico/In Vitro hit-to-lead methodology yields SMYD3 inhibitor that eliminates unrestrained proliferation of breast carcinoma cells. Int. J. Mol. Sci. 21(24). doi: 10.3390/ijms21249549

Berger, S.L. 2007. The complex language of chromatin regulation during transcription. Nature 447(7143): 407-412. doi: 10.1038/nature05915

Berkholz, J., Orgeur, M., Stricker, S. & Munz, B. 2015. skNAC and SMYD1 in transcriptional control. Exp. Cell Res. 336(2): 182-191. doi: 10.1016/j.yexcr.2015.06.019

Binh, M.T., Hoan, N.X., Giang, D.P., Tong, H.V., Bock, C.T., Wedemeyer, H., Toan, N.L., Bang, M.H., Kremsner, P.G., Meyer, C.G., Song, L.H. & Velavan, T.P. 2020. Upregulation of SMYD3 and SMYD3 VNTR 3/3 polymorphism increase the risk of hepatocellular carcinoma. Sci. Rep. 10(1): 2797. doi: 10.1038/s41598-020-59667-z

Brown, M.A., Edwards, M.A., Alshiraihi, I., Geng, H., Dekker, J.D. & Tucker, H.O. 2020. The lysine methyltransferase SMYD2 is required for normal lymphocyte development and survival of hematopoietic leukemias. Genes Immun. 21(2): 119-130. doi: 10.1038/s41435-020-0094-8

Brown, M.A., Sims 3rd., R.J., Gottlieb, P.D. & Tucker, P.W. 2006. Identification and characterization of SMYD2: A split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex. Mol. Cancer 5: 26. doi: 10.1186/1476-4598-5-26

Carlson, S.M. & Gozani, O. 2016. Nonhistone lysine methylation in the regulation of cancer pathways. Cold Spring Harbor Perspectives in Medicine 6(11): a026435.

Chandra, P., Dixit, R., Pratap, A., Mishra, S., Mishra, R. & Shukla, V.K. 2021. Analysis of SET and MYND domain-containing protein 3 (SMYD3) expression in gallbladder cancer: A pilot study. Indian J. Surg. Oncol. 12(Suppl 1): 111-117. doi: 10.1007/s13193-020-01168-6

Chen, D., Liu, L., Luo, X., Mu, A., Yan, L., Chen, X., Wang, L., Wang, N., He, H., Zhou, H. & Zhang, T. 2017. Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells. Oncol. Lett. 14(2): 1831-1840. doi: 10.3892/ol.2017.6320

Chen, L.B., Xu, J.Y., Yang, Z. & Wang, G.B. 2007. Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration. World J. Gastroenterol. 13(43): 5718-5724. doi: 10.3748/wjg.v13.i43.5718

Cho, H.S., Hayami, S., Toyokawa, G., Maejima, K., Yamane, Y., Suzuki, T., Dohmae, N., Kogure, M., Kang, D., Neal, D.E., Ponder, B.A., Yamaue, H., Nakamura, Y. & Hamamoto, R. 2012. RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation. Neoplasia 14(6): 476-486. doi: 10.1593/neo.12656

Cowen, S.D., Russell, D., Dakin, L.A., Chen, H., Larsen, N.A., Godin, R. & Ferguson, A.D. 2016. Design, synthesis, and biological activity of substrate competitive SMYD2 inhibitors. Journal of Medicinal Chemistry 59(24): 11079-11097.

Dai, B., Wan, W., Zhang, P., Zhang, Y., Pan, C., Meng, G., Xiao, X., Wu, Z., Jia, W., Zhang, J. & Zhang, L. 2015. SET and MYND domain-containing protein 3 is overexpressed in human glioma and contributes to tumorigenicity. Oncol. Rep. 34(5): 2722-2730. doi: 10.3892/or.2015.4239

Deng, X., Hamamoto, R., Vougiouklakis, T., Wang, R., Yoshioka, Y., Suzuki, T., Dohmae, N., Matsuo, Y., Park, J.H. & Nakamura, Y. 2017. Critical roles of SMYD2-mediated beta-catenin methylation for nuclear translocation and activation of Wnt signaling. Oncotarget 8(34): 55837-55847. doi: 10.18632/oncotarget.19646

Dong, S.W., Zhang, H., Wang, B.L., Sun, P., Wang, Y.G. & Zhang, P. 2014. Effect of the downregulation of SMYD3 expression by RNAi on RIZ1 expression and proliferation of esophageal squamous cell carcinoma. Oncol. Rep. 32(3): 1064-1070. doi: 10.3892/or.2014.3307

Donlin, L.T., Andresen, C., Just, S., Rudensky, E., Pappas, C.T., Kruger, M.E.Y., Unger, J.A., Zieseniss, A., Dobenecker, M.W., Voelkel, T., Chait, B.T., Gregorio, C.C., Rottbauer, W., Tarakhovsky, A. & Linke, W.A. 2012. SMYD2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization. Genes Dev. 26(2): 114-119. doi: 10.1101/gad.177758.111

Du, S.J., Tan, X. & Zhang, J. 2014. SMYD proteins: Key regulators in skeletal and cardiac muscle development and function. Anat. Rec. (Hoboken) 297(9): 1650-1662. doi: 10.1002/ar.22972

Fei, X., Ma, Y., Liu, X. & Meng, Z. 2017. Overexpression of SMYD3 is predictive of unfavorable prognosis in hepatocellular carcinoma. Tohoku J. Exp. Med. 243(3): 219-226. doi: 10.1620/tjem.243.219

Fenizia, C., Bottino, C., Corbetta, S., Fittipaldi, R., Floris, P., Gaudenzi, G., Carra, S., Cotelli, F., Vitale, G. & Caretti, G. 2019. SMYD3 promotes the epithelial-mesenchymal transition in breast cancer. Nucleic Acids Res. 47(3): 1278-1293. doi: 10.1093/nar/gky1221

Ferguson, A.D., Larsen, N.A., Howard, T., Pollard, H., Green, I., Grande, C., Cheung, T., Garcia-Arenas, R., Cowen, S., Wu, J., Godin, R., Chen, H. & Keen, N. 2011. Structural basis of substrate methylation and inhibition of SMYD2. Structure 19(9): 1262-1273. doi: 10.1016/j.str.2011.06.011

Flavahan, W.A., Gaskell, E. & Bernstein, B.E. 2017. Epigenetic plasticity and the hallmarks of cancer. Science 357(6348): eaal2380. doi: 10.1126/science.aal2380

Foreman, K.W., Brown, M., Park, F., Emtage, S., Harriss, J., Das, C., Zhu, L., Crew, A., Arnold, L., Shaaban, S. & Tucker, P. 2011. Structural and functional profiling of the human histone methyltransferase SMYD3. PLoS ONE 6(7): e22290. doi: 10.1371/journal.pone.0022290

Gottlieb, P.D., Pierce, S.A., Sims, R.J., Yamagishi, H., Weihe, E.K., Harriss, J.V., Maika, S.D., Kuziel, W.A., King, H.L., Olson, E.N., Nakagawa, O. & Srivastava, D. 2002. Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat. Genet. 31(1): 25-32. doi: 10.1038/ng866

Guo, N., Chen, R., Li, Z., Liu, Y., Cheng, D., Zhou, Q., Zhou, J. & Lin, Q. 2011. Hepatitis C virus core upregulates the methylation status of the RASSF1A promoter through regulation of SMYD3 in hilar cholangiocarcinoma cells. Acta Biochim. Biophys. Sin. (Shanghai) 43(5): 354-361. doi: 10.1093/abbs/gmr021

Hamamoto, R., Furukawa, Y., Morita, M., Iimura, Y., Silva, F.P., Li, M., Yagyu, R. & Nakamura, Y. 2004. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. Cell Biol. 6(8): 731-740. doi: 10.1038/ncb1151

Hamamoto, R., Silva, F.P., Tsuge, M., Nishidate, T., Katagiri, T., Nakamura, Y. & Furukawa, Y. 2006. Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci. 97(2): 113-118. doi: 10.1111/j.1349-7006.2006.00146.x

Hamamoto, R., Toyokawa, G., Nakakido, M., Ueda, K. & Nakamura, Y. 2014. SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. Cancer Lett. 351(1): 126-133. doi: 10.1016/j.canlet.2014.05.014

Han, S., Zou, H., Lee, J.W., Han, J., Kim, H.C., Cheol, J.J., Kim, L.S. & Kim, H. 2019. miR-1307-3p stimulates breast cancer development and progression by targeting SMYD4. J. Cancer 10(2): 441-448. doi: 10.7150/jca.30041

Hu, L., Zhu, Y.T., Qi, C. & Zhu, Y.J. 2009. Identification of SMYD4 as a potential tumor suppressor gene involved in breast cancer development. Cancer Res. 69(9): 4067-4072. doi: 10.1158/0008-5472.CAN-08-4097

Huang, J., Perez-Burgos, L., Placek, B.J., Sengupta, R., Richter, M., Dorsey, J.A., Kubicek, S., Opravil, S., Jenuwein, T. & Berger, S.L. 2006. Repression of p53 activity by SMYD2-mediated methylation. Nature 444(7119): 629-632. doi: 10.1038/nature05287

Huang, L. & Xu, A.M. 2017. SET and MYND domain containing protein 3 in cancer. Am. J. Transl. Res. 9(1): 1-14.

Hwang, I. & Gottlieb, P.D. 1995. Bop: A new T-cell-restricted gene located upstream of and opposite to mouse CD8b. Immunogenetics 42(5): 353-361. doi: 10.1007/bf00179396

Jiang, Y., Lyu, T., Che, X., Jia, N., Li, Q. & Feng, W. 2019. Overexpression of SMYD3 in ovarian cancer is associated with ovarian cancer proliferation and apoptosis via methylating H3K4 and H4K20. J. Cancer 10(17): 4072-4084. doi: 10.7150/jca.29861

Jiang, Y., Trescott, L., Holcomb, J., Zhang, X., Brunzelle, J., Sirinupong, N., Shi, X. & Yang, Z. 2014. Structural insights into estrogen receptor alpha methylation by histone methyltransferase SMYD2, a cellular event implicated in estrogen signaling regulation. J. Mol. Biol. 426(20): 3413-3425. doi: 10.1016/j.jmb.2014.02.019

Kawamura, S., Yoshigai, E., Kuhara, S. & Tashiro, K. 2008. SMYD1 and SMYD2 are expressed in muscle tissue in Xenopus laevis. Cytotechnology 57(2): 161-168. doi: 10.1007/s10616-008-9128-1

Kidder, B.L., He, R., Wangsa, D., Padilla-Nash, H.M., Bernardo, M.M., Sheng, S., Ried, T. & Zhao, K. 2017. SMYD5 controls heterochromatin and chromosome integrity during embryonic stem cell differentiation. Cancer Res. 77(23): 6729-6745. doi: 10.1158/0008-5472.CAN-17-0828

Kidder, B.L., Hu, G., Cui, K. & Zhao, K. 2017. SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation. Epigenetics Chromatin 10: 8. doi: 10.1186/s13072-017-0115-7

Kim, H., Heo, K., Kim, J.H., Kim, K., Choi, J. & An, W. 2009. Requirement of histone methyltransferase SMYD3 for estrogen receptor-mediated transcription. J. Biol. Chem. 284(30): 19867-19877. doi: 10.1074/jbc.M109.021485

Kojima, M., Sone, K., Oda, K., Hamamoto, R., Kaneko, S., Oki, S., Kukita, A., Kawata, A., Honjoh, H., Kawata, Y., Kashiyama, T., Sato, M., Taguchi, A., Miyamoto, Y., Tanikawa, M., Tsuruga, T., Nagasaka, K., Wada-Hiraike, O., Osuga, Y. & Fujii, T. 2020. The histone methyltransferase SMYD2 is a novel therapeutic target for the induction of apoptosis in ovarian clear cell carcinoma cells. Oncol. Lett. 20(5): 153. doi: 10.3892/ol.2020.12014

Komatsu, S., Ichikawa, D., Hirajima, S., Nagata, H., Nishimura, Y., Kawaguchi, T., Miyamae, M., Okajima, W., Ohashi, T., Konishi, H., Shiozaki, A., Fujiwara, H., Okamoto, K., Tsuda, H., Imoto, I., Inazawa, J. & Otsuji, E. 2015. Overexpression of SMYD2 contributes to malignant outcome in gastric cancer. Br. J. Cancer 112(2): 357-364. doi: 10.1038/bjc.2014.543

Komatsu, S., Imoto, I., Tsuda, H., Kozaki, K.I., Muramatsu, T., Shimada, Y., Aiko, S., Yoshizumi, Y., Ichikawa, D., Otsuji, E. & Inazawa, J. 2009. Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. Carcinogenesis 30(7): 1139-1146. doi: 10.1093/carcin/bgp116

Kontaki, H., Koukaki, M., Vasilarou, M., Giakountis, A., Deligianni, E., Luo, X., Kim, Y. & Talianidis, I. 2021. Targeting SMYD3 by next-generation antisense oligonucleotides suppresses liver tumor growth. iScience 24(5): 102473. doi: 10.1016/j.isci.2021.102473

Kukita, A., Sone, K., Oda, K., Hamamoto, R., Kaneko, S., Komatsu, M., Wada, M., Honjoh, H., Kawata, Y., Kojima, M., Oki, S., Sato, M., Asada, K., Taguchi, A., Miyasaka, A., Tanikawa, M., Nagasaka, K., Matsumoto, Y., Wada-Hiraike, O., Osuga, Y. & Fujii, T. 2019. Histone methyltransferase SMYD2 selective inhibitor LLY-507 in combination with poly ADP ribose polymerase inhibitor has therapeutic potential against high-grade serous ovarian carcinomas. Biochem. Biophys. Res. Commun. 513(2): 340-346. doi: 10.1016/j.bbrc.2019.03.155

Kunizaki, M., Hamamoto, R., Silva, F.P., Yamaguchi, K., Nagayasu, T., Shibuya, M., Nakamura, Y. & Furukawa, Y. 2007. The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. Cancer Res. 67(22): 10759-10765. doi: 10.1158/0008-5472.CAN-07-1132

Lanouette, S., Davey, J.A., Elisma, F., Ning, Z., Figeys, D., Chica, R.A. & Couture, J.F. 2015. Discovery of substrates for a SET domain lysine methyltransferase predicted by multistate computational protein design. Structure 23(1): 206-215. doi: 10.1016/j.str.2014.11.004

Leinhart, K. & Brown, M. 2011. SET/MYND lysine methyltransferases regulate gene transcription and protein activity. Genes (Basel) 2(1): 210-218. doi: 10.3390/genes2010210

Lenkiewicz, E., Malasi, S., Hogenson, T.L., Flores, L.F., Barham, W., Phillips, W.J., Roesler, A.S., Chambers, K.R., Rajbhandari, N., Hayashi, A., Antal, C.E., Downes, M., Grandgenett, P.M., Hollingsworth, M.A., Cridebring, D., Xiong, Y., Lee, J.H., Ye, Z., Yan, H., Hernandez, M.C., Leiting, J.L., Evans, R.M., Ordog, T., Truty, M.J., Borad, M.J., Reya, T., Von Hoff, D.D., Fernandez-Zapico, M.E. & Barrett, M.T. 2020. Genomic and epigenomic landscaping defines new therapeutic targets for adenosquamous carcinoma of the pancreas. Cancer Res. 80(20): 4324-4334. doi: 10.1158/0008-5472.CAN-20-0078

Li, B., Pan, R., Zhou, C., Dai, J., Mao, Y., Chen, M., Huang, T., Ying, X., Hu, H., Zhao, J., Zhang, W. & Duan, S. 2018. SMYD3 promoter hypomethylation is associated with the risk of colorectal cancer. Future Oncol. 14(18): 1825-1834. doi: 10.2217/fon-2017-0682

Li, J., Zhao, L., Pan, Y., Ma, X., Liu, L., Wang, W. & You, W. 2020. SMYD3 overexpression indicates poor prognosis and promotes cell proliferation, migration and invasion in nonsmall cell lung cancer. Int. J. Oncol. 57(3): 756-766. doi: 10.3892/ijo.2020.5095

Li, L.X., Zhou, J.X., Wang, X., Zhang, H., Harris, P.C., Calvet, J.P. & Li, X. 2020. Cross-talk between CDK4/6 and SMYD2 regulates gene transcription, tubulin methylation, and ciliogenesis. Sci. Adv. 6(44). doi: 10.1126/sciadv.abb3154

Li, R.D., Tang, Y.H., Wang, H.L., Yang, D., Sun, L.J. & Li, W. 2018. The SMYD3 VNTR 3/3 polymorphism confers an increased risk and poor prognosis of hepatocellular carcinoma in a Chinese population. Pathol. Res. Pract. 214(5): 625-630. doi: 10.1016/j.prp.2018.04.005

Lin, F., Wu, D., Fang, D., Chen, Y., Zhou, H. & Ou, C. 2019. STAT3-induced SMYD3 transcription enhances chronic lymphocytic leukemia cell growth in vitro and in vivo. Inflamm. Res. 68(9): 739-749. doi: 10.1007/s00011-019-01257-5

Liu, C., Liu, L., Wang, K., Li, X.F., Ge, L.Y., Ma, R.Z., Fan, Y.D., Li, L.C., Liu, Z.F., Qiu, M., Hao, Y.C., Shi, Z.F., Xia, C.Y., Straat, K., Huang, Y., Ma, L.L. & Xu, D. 2020. VHL-HIF-2alpha axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR. Oncogene 39(21): 4286-4298. doi: 10.1038/s41388-020-1291-7

Liu, H., Liu, Y., Kong, F., Xin, W., Li, X., Liang, H. & Jia, Y. 2015. Elevated levels of SET and MYND domain-containing protein 3 are correlated with overexpression of transforming growth factor-beta1 in gastric cancer. J. Am. Coll. Surg. 221(2): 579-590. doi: 10.1016/j.jamcollsurg.2015.02.023

Liu, X., Zheng, Z., Chen, C., Guo, S., Liao, Z., Li, Y., Zhu, Y., Zou, H., Wu, J., Xie, W., Zhang, P., Xu, L., Wu, B. & Li, E. 2017. Network analyses elucidate the role of SMYD3 in esophageal squamous cell carcinoma. FEBS Open Bio 7(8): 1111-1125. doi: 10.1002/2211-5463.12251

Liu, Y., Chen, W., Gaudet, J., Cheney, M.D., Roudaia, L., Cierpicki, T., Klet, R.C., Hartman, K., Laue, T.M., Speck, N.A. & Bushweller, J.H. 2007. Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity. Cancer Cell 11(6): 483-497. doi: 10.1016/j.ccr.2007.04.010

Liu, Y., Deng, J., Luo, X., Pan, Y., Zhang, L., Zhang, R. & Liang, H. 2015. Overexpression of SMYD3 was associated with increased STAT3 activation in gastric cancer. Med. Oncol. 32(1): 404. doi: 10.1007/s12032-014-0404-y

Liu, Y., Liu, H., Luo, X., Deng, J., Pan, Y. & Liang, H. 2015. Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer. Tumour Biol. 36(6): 4377-4386. doi: 10.1007/s13277-015-3077-z

Liu, Y., Luo, X., Deng, J., Pan, Y., Zhang, L. & Liang, H. 2015. SMYD3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma. Tumour Biol. 36(4): 2685-2694. doi: 10.1007/s13277-014-2891-z

Lobo, J., Rodrigues, A., Antunes, L., Graca, I., Ramalho-Carvalho, J., Vieira, F.Q., Martins, A.T., Oliveira, J., Jeronimo, C. & Henrique, R. 2018. High immunoexpression of Ki67, EZH2, and SMYD3 in diagnostic prostate biopsies independently predicts outcome in patients with prostate cancer. Urol. Oncol. 36(4): 161.e7-161.e17. doi: 10.1016/j.urolonc.2017.10.028

Luo, X.G., Zhang, C.L., Zhao, W.W., Liu, Z.P., Liu, L., Mu, A., Guo, S., Wang, N., Zhou, H. & Zhang, T.C. 2014. Histone methyltransferase SMYD3 promotes MRTF-A-mediated transactivation of MYL9 and migration of MCF-7 breast cancer cells. Cancer Lett. 344 (1): 129-137. doi: 10.1016/j.canlet.2013.10.026

Lyu, T., Jiang, Y., Jia, N., Che, X., Li, Q., Yu, Y., Hua, K., Bast Jr., R.C. & Feng, W. 2019. SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters. Int. J. Cancer. doi: 10.1002/ijc.32673

Lyu, T., Jiang, Y., Jia, N., Che, X., Li, Q., Yu, Y., Hua, K., Bast Jr., R.C. & Feng, W. 2020. SMYD3 promotes implant metastasis of ovarian cancer via H3K4 trimethylation of integrin promoters. Int. J. Cancer 146(6): 1553-1567. doi: 10.1002/ijc.32673

Ma, S.J., Liu, Y.M., Zhang, Y.L., Chen, M.W. & Cao, W. 2018. Correlations of EZH2 and SMYD3 gene polymorphisms with breast cancer susceptibility and prognosis. Biosci. Rep. 38(1). doi: 10.1042/BSR20170656

Mann, M. & Jensen, O.N. 2003. Proteomic analysis of post-translational modifications. Nat. Biotechnol. 21(3): 255-261. doi: 10.1038/nbt0303-255

Mazur, P.K., Reynoird, N., Khatri, P., Jansen, P.W., Wilkinson, A.W., Liu, S., Barbash, O., Van Aller, G.S., Huddleston, M., Dhanak, D., Tummino, P.J., Kruger, R.G., Garcia, B.A., Butte, A.J., Vermeulen, M., Sage, J. & Gozani, O. 2014. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 510(7504): 283-287. doi: 10.1038/nature13320

Nakakido, M., Deng, Z., Suzuki, T., Dohmae, N., Nakamura, Y. & Hamamoto, R. 2015. Dysregulation of AKT pathway by SMYD2-Mediated lysine methylation on PTEN. Neoplasia 17(4): 367-373. doi: 10.1016/j.neo.2015.03.002

Ohtomo-Oda, R., Komatsu, S., Mori, T., Sekine, S., Hirajima, S., Yoshimoto, S., Kanai, Y., Otsuji, E., Ikeda, E. & Tsuda, H. 2016. SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. Hum. Pathol. 49: 145-155. doi: 10.1016/j.humpath.2015.08.025

Oliveira-Santos, W., Rabello, D.A., Lucena-Araujo, A.R., de Oliveira, F.M., Rego, E.M., Pittella Silva, F. & Saldanha-Araujo, F. 2016. Residual expression of SMYD2 and SMYD3 is associated with the acquisition of complex karyotype in chronic lymphocytic leukemia. Tumour Biol. 37(7): 9473-9481. doi: 10.1007/s13277-016-4846-z

Olsen, J.B., Cao, X.J., Han, B., Chen, L.H., Horvath, A., Richardson, T.I., Campbell, R.M., Garcia, B.A. & Nguyen, H. 2016. Quantitative profiling of the activity of protein lysine methyltransferase SMYD2 using SILAC-based proteomics. Mol. Cell Proteomics 15(3): 892-905. doi: 10.1074/mcp.M115.053280

Peserico, A., Germani, A., Sanese, P., Barbosa, A.J., Di Virgilio, V., Fittipaldi, R., Fabini, E., Bertucci, C., Varchi, G., Moyer, M.P., Caretti, G., Del Rio, A. & Simone, C. 2015. A SMYD3 small-molecule inhibitor impairing cancer cell growth. J. Cell Physiol. 230(10): 2447-2460. doi: 10.1002/jcp.24975

Phan, D., Rasmussen, T.L., Nakagawa, O., McAnally, J., Gottlieb, P.D., Tucker, P.W., Richardson, J.A., Bassel-Duby, R. & Olson, E.N. 2005. BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart. Development 132(11): 2669-2678. doi: 10.1242/dev.01849

Piao, L., Kang, D., Suzuki, T., Masuda, A., Dohmae, N., Nakamura, Y. & Hamamoto, R. 2014. The histone methyltransferase SMYD2 methylates PARP1 and promotes poly(ADP-ribosyl)ation activity in cancer cells. Neoplasia 16(3): 257-264, 264.e2. doi: 10.1016/j.neo.2014.03.002

Rasmussen, T.L., Ma, Y., Park, C.Y., Harriss, J., Pierce, S.A., Dekker, J.D., Valenzuela, N., Srivastava, D., Schwartz, R.J., Stewart, M.D. & Tucker, H.O. 2015. SMYD1 facilitates heart development by antagonizing oxidative and ER stress responses. PLoS ONE 10(3): e0121765. doi: 10.1371/journal.pone.0121765

Rea, S., Eisenhaber, F., O'Carroll, D., Strahl, B.D., Sun, Z.W., Schmid, M., Opravil, S., Mechtler, K., Ponting, C.P., Allis, C.D. & Jenuwein, T. 2000. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406(6796): 593-599. doi: 10.1038/35020506

Ren, H., Wang, Z., Chen, Y., Liu, Y., Zhang, S., Zhang, T. & Li, Y. 2019. SMYD2-OE promotes oxaliplatin resistance in colon cancer through MDR1/P-glycoprotein via MEK/ERK/AP1 pathway. Onco. Targets Ther. 12: 2585-2594. doi: 10.2147/OTT.S186806

Ren, T.N., Wang, J.S., He, Y.M., Xu, C.L., Wang, S.Z. & Xi, T. 2011. Effects of SMYD3 over-expression on cell cycle acceleration and cell proliferation in MDA-MB-231 human breast cancer cells. Med. Oncol. 28(Suppl 1): S91-S98). doi: 10.1007/s12032-010-9718-6

Reynoird, N., Mazur, P.K., Stellfeld, T., Flores, N.M., Lofgren, S.M., Carlson, S.M., Brambilla, E., Hainaut, P., Kaznowska, E.B., Arrowsmith, C.H., Khatri, P., Stresemann, C., Gozani, O. & Sage, J. 2016. Coordination of stress signals by the lysine methyltransferase SMYD2 promotes pancreatic cancer. Genes Dev. 30(7): 772-785. doi: 10.1101/gad.275529.115

Rubio-Tomás, T. 2021. The SMYD family proteins in immunology: An update of their obvious and non-obvious relations with the immune system. Heliyon 7(6): e07387.

Saddic, L.A., West, L.E., Aslanian, A., Yates 3rd., J.R., Rubin, S.M., Gozani, O. & Sage, J. 2010. Methylation of the retinoblastoma tumor suppressor by SMYD2. J. Biol. Chem. 285(48): 37733-37740. doi: 10.1074/jbc.M110.137612

Sajjad, A., Novoyatleva, T., Vergarajauregui, S., Troidl, C., Schermuly, R.T., Tucker, H.O. & Engel, F.B. 2014. Lysine methyltransferase SMYD2 suppresses p53-dependent cardiomyocyte apoptosis. Biochim Biophys Acta 1843(11): 2556-2562. doi: 10.1016/j.bbamcr.2014.06.019

Sakamoto, L.H., Andrade, R.V., Felipe, M.S., Motoyama, A.B. & Pittella Silva, F. 2014. SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor. Leuk. Res. 38(4): 496-502. doi: 10.1016/j.leukres.2014.01.013

Sampieri, C.L., de la Pena, S., Ochoa-Lara, M., Zenteno-Cuevas, R. & Leon-Cordoba, K. 2010. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World J. Gastroenterol. 16(12): 1500-1505. doi: 10.3748/wjg.v16.i12.1500

Sarfraz, I., Rasul, A., Hussain, G., Shah, M.A., Zahoor, A.F., Asrar, M., Selamoglu, Z., Ji, X.Y., Adem, S. & Sarker, S.D. 2020. 6-Phosphogluconate dehydrogenase fuels multiple aspects of cancer cells: From cancer initiation to metastasis and chemoresistance. Biofactors. doi: 10.1002/biof.1624

Sarfraz, I., Rasul, A., Hussain, G., Hussain, S.M., Ahmad, M., Nageen, B., Jabeen, F., Selamoglu, Z. & Ali, M. 2018. Malic enzyme 2 as a potential therapeutic drug target for cancer. IUBMB Life 70(11): 1076-1083. doi: 10.1002/iub.1930

Shang, L. & Wei, M. 2019. Inhibition of SMYD2 sensitized cisplatin to resistant cells in NSCLC through activating p53 pathway. Front Oncol. 9: 306. doi: 10.3389/fonc.2019.00306

Sharif, F., Rasul, A., Ashraf, A., Hussain, G., Younis, T., Sarfraz, I., Chaudhry, M.A., Bukhari, S.A., Ji, X.Y., Selamoglu, Z. & Ali, M. 2019. Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy. IUBMB Life 71(10): 1418-1427. doi: 10.1002/iub.2100

Shen, B., Tan, M., Mu, X., Qin, Y., Zhang, F., Liu, Y. & Fan, Y. 2016. Upregulated SMYD3 promotes bladder cancer progression by targeting BCLAF1 and activating autophagy. Tumour Biol. 37(6): 7371-7381. doi: 10.1007/s13277-015-4410-2

Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A., Casero, R.A. & Shi, Y. 2004. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119(7): 941-953. doi: 10.1016/j.cell.2004.12.012

Sirinupong, N., Brunzelle, J., Doko, E. & Yang, Z. 2011. Structural insights into the autoinhibition and posttranslational activation of histone methyltransferase SMYD3. J. Mol. Biol. 406(1): 149-159. doi: 10.1016/j.jmb.2010.12.014

Sirinupong, N., Brunzelle, J., Ye, J., Pirzada, A., Nico, L. & Yang, Z. 2010. Crystal structure of cardiac-specific histone methyltransferase SMYD1 reveals unusual active site architecture. J. Biol. Chem. 285(52): 40635-40644. doi: 10.1074/jbc.M110.168187

Song, J., Liu, Y., Chen, Q., Yang, J., Jiang, Z., Zhang, H., Liu, Z. & Jin, B. 2019. Expression patterns and the prognostic value of the SMYD family members in human breast carcinoma using integrative bioinformatics analysis. Oncol. Lett. 17(4): 3851-3861. doi: 10.3892/ol.2019.10054

Spellmon, N., Holcomb, J., Trescott, L., Sirinupong, N. & Yang, Z. 2015. Structure and function of SET and MYND domain-containing proteins. Int. J. Mol. Sci. 16(1): 1406-1428. doi: 10.3390/ijms16011406

Stender, J.D., Pascual, G., Liu, W., Kaikkonen, M.U., Do, K., Spann, N.J., Boutros, M., Perrimon, N., Rosenfeld, M.G. & Glass, C.K. 2012. Control of proinflammatory gene programs by regulated trimethylation and demethylation of histone H4K20. Mol. Cell 48(1): 28-38. doi: 10.1016/j.molcel.2012.07.020

Sun, J.J., Li, H.L., Ma, H., Shi, Y., Yin, L.R. & Guo, S.J. 2019. SMYD2 promotes cervical cancer growth by stimulating cell proliferation. Cell Biosci. 9: 75. doi: 10.1186/s13578-019-0340-9

Tan, X., Rotllant, J., Li, H., De Deyne, P. & Du, S.J. 2006. SMYD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos. Proc. Natl. Acad. Sci. U.S.A. 103(8): 2713-2718. doi: 10.1073/pnas.0509503103

Tracy, C., Warren, J.S., Szulik, M., Wang, L., Garcia, J., Makaju, A., Russell, K., Miller, M. & Franklin, S. 2018. The SMYD family of methyltransferases: Role in cardiac and skeletal muscle physiology and pathology. Curr. Opin. Physiol. 1: 140-152. doi: 10.1016/j.cophys.2017.10.001

Tomás, T.R. 2021. SMYD2 in Leukemia: An update. Int. J. Blood Res. Disord8: 067.

Van Aller, G.S., Reynoird, N., Barbash, O., Huddleston, M., Liu, S., Zmoos, A.F., McDevitt, P., Sinnamon, R., Le, B., Mas, G., Annan, R., Sage, J., Garcia, B.A., Tummino, P.J., Gozani, O. & Kruger, R.G. 2012. SMYD3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics 7(4): 340-343. doi: 10.4161/epi.19506

Vieira, F.Q., Costa-Pinheiro, P., Almeida-Rios, D., Graca, I., Monteiro-Reis, S., Simoes-Sousa, S., Carneiro, I., Sousa, E.J., Godinho, M.I., Baltazar, F., Henrique, R. & Jeronimo, C. 2015. SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3. Oncotarget 6(15): 13644-13657. doi: 10.18632/oncotarget.3767

Wang, G., Huang, Y., Yang, F., Tian, X., Wang, K., Liu, L., Fan, Y., Li, X., Li, L., Shi, B., Hao, Y., Xia, C., Nie, Q., Xin, Y., Shi, Z., Ma, L., Xu, D. & Liu, C. 2020. High expression of SMYD3 indicates poor survival outcome and promotes tumour progression through an IGF-1R/AKT/E2F-1 positive feedback loop in bladder cancer. Aging (Albany NY) 12(3): 2030-2048. doi: 10.18632/aging.102718

Wang, H., Liu, Y., Tan, W., Zhang, Y., Zhao, N., Jiang, Y., Lin, C., Hao, B., Zhao, D., Qian, J., Lu, D., Jin, L., Wei, Q., Lin, D. & He, F. 2008. Association of the variable number of tandem repeats polymorphism in the promoter region of the SMYD3 gene with risk of esophageal squamous cell carcinoma in relation to tobacco smoking. Cancer Sci. 99(4): 787-791. doi: 10.1111/j.1349-7006.2008.00729.x

Wang, L., Wang, Q.T., Liu, Y.P., Dong, Q.Q., Hu, H.J., Miao, Z., Li, S., Liu, Y., Zhou, H., Zhang, T.C., Ma, W.J. & Luo, X.G. 2017. ATM signaling pathway is implicated in the SMYD3-mediated proliferation and migration of gastric cancer cells. J. Gastric Cancer 17(4): 295-305. doi: 10.5230/jgc.2017.17.e33

Wang, R., Deng, X., Yoshioka, Y., Vougiouklakis, T., Park, J.H., Suzuki, T., Dohmae, N., Ueda, K., Hamamoto, R. & Nakamura, Y. 2017. Effects of SMYD2-mediated EML4-ALK methylation on the signaling pathway and growth in non-small-cell lung cancer cells. Cancer Sci. 108(6): 1203-1209. doi: 10.1111/cas.13245

Wang, S.Z., Luo, X.G., Shen, J., Zou, J.N., Lu, Y.H. & Xi, T. 2008. Knockdown of SMYD3 by RNA interference inhibits cervical carcinoma cell growth and invasion in vitro. BMB Rep. 41(4): 294-299. doi: 10.5483/bmbrep.2008.41.4.294

Wu, X., Xu, Q., Chen, P., Yu, C., Ye, L., Huang, C. & Li, T. 2019. Effect of SMYD3 on biological behavior and H3K4 methylation in bladder cancer. Cancer Manag. Res. 11: 8125-8133. doi: 10.2147/CMAR.S213885

Xu, W., Chen, F., Fei, X., Yang, X. & Lu, X. 2018. Overexpression of SET and MYND domain-containing protein 2 (SMYD2) is associated with tumor progression and poor prognosis in patients with papillary thyroid carcinoma. Med. Sci. Monit. 24: 7357-7365. doi: 10.12659/MSM.910168

Yan, L., Ding, B., Liu, H., Zhang, Y., Zeng, J., Hu, J., Yao, W., Yu, G., An, R., Chen, Z., Ye, Z., Xing, J., Xiao, K., Wu, L. & Xu, H. 2019. Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma. Theranostics 9(26): 8377-8391. doi: 10.7150/thno.37628

Yang, D., Wang, Q., Wei, G., Wu, J., Zhu, Y.C., Zhu, Q., Ni, T., Liu, X. & Zhu, Y.Z. 2020. SMYD3-PARP16 axis accelerates unfolded protein response and vascular aging. Aging (Albany NY) 12(21): 21423-21445. doi: 10.18632/aging.103895

Yang, L., He, J., Chen, L. & Wang, G. 2009. Hepatitis B virus X protein upregulates expression of SMYD3 and C-MYC in HepG2 cells. Med. Oncol. 26(4): 445-451. doi: 10.1007/s12032-008-9144-1

Yoo, C.B. & Jones, P.A. 2006. Epigenetic therapy of cancer: past, present and future. Nat. Rev. Drug Discov. 5(1): 37-50. doi: 10.1038/nrd1930

Yue, F.R., Wei, Z.B., Yan, R.Z., Guo, Q.H., Liu, B., Zhang, J.H. & Li, Z. 2020. SMYD3 promotes colon adenocarcinoma (COAD) progression by mediating cell proliferation and apoptosis. Exp. Ther. Med. 20(5): 11. doi: 10.3892/etm.2020.9139

Zeng, B., Li, Z., Chen, R., Guo, N., Zhou, J., Zhou, Q., Lin, Q., Cheng, D., Liao, Q., Zheng, L. & Gong, Y. 2012. Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3. FEBS Lett. 586(19): 3271-3278. doi: 10.1016/j.febslet.2012.06.049

Zeng, Y., Qiu, R., Yang, Y., Gao, T., Zheng, Y., Huang, W., Gao, J., Zhang, K., Liu, R., Wang, S., Hou, Y., Yu, W., Leng, S., Feng, D., Liu, W., Zhang, X. & Wang, Y. 2019. Regulation of EZH2 by SMYD2-Mediated lysine methylation is implicated in tumorigenesis. Cell Rep. 29(6): 1482-1498.e4. doi: 10.1016/j.celrep.2019.10.004

Zhang, H., Zheng, Z., Zhang, R., Yan, Y., Peng, Y., Ye, H. & Huang, P. 2021. SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters. Cell Death & Disease 12(8): 1-10.

Zhang, L., Jin, Y., Yang, H., Li, Y., Wang, C., Shi, Y. & Wang, Y. 2019a. SMYD3 promotes epithelial ovarian cancer metastasis by down-regulating p53 protein stability and promoting p53 ubiquitination. Carcinogenesis. doi: 10.1093/carcin/bgz078

Zhang, L., Jin, Y., Yang, H., Li, Y., Wang, C., Shi, Y. & Wang, Y. 2019b. SMYD3 promotes epithelial ovarian cancer metastasis by downregulating p53 protein stability and promoting p53 ubiquitination. Carcinogenesis 40(12): 1492-1503. doi: 10.1093/carcin/bgz078

Zhang, P., Ruan, J., Weng, W. & Tang, Y. 2020. Overexpression of SET and MYND domain-containing protein 2 (SMYD2) is associated with poor prognosis in pediatric B lineage acute lymphoblastic leukemia. Leuk Lymphoma 61(2): 437-444. doi: 10.1080/10428194.2019.1675875

Zhang, X.D., Huang, G.W., Xie, Y.H., He, J.Z., Guo, J.C., Xu, X.E., Liao, L.D., Xie, Y.M., Song, Y.M., Li, E.M. & Xu, L.Y. 2018. The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells. Nucleic Acids Res. 46(4): 1793-1809. doi: 10.1093/nar/gkx1259

Zhang, X., Tanaka, K., Yan, J., Li, J., Peng, D., Jiang, Y., Yang, Z., Barton, M.C., Wen, H. & Shi, X. 2013. Regulation of estrogen receptor alpha by histone methyltransferase SMYD2-mediated protein methylation. Proc. Natl. Acad. Sci. U.S.A. 110(43): 17284-17289. doi: 10.1073/pnas.1307959110

Zhou, Z., Jiang, H., Tu, K., Yu, W., Zhang, J., Hu, Z., Zhang, H., Hao, D., Huang, P., Wang, J., Wang, A., Xiao, Z. & He, C. 2019. ANKHD1 is required for SMYD3 to promote tumor metastasis in hepatocellular carcinoma. J. Exp. Clin. Cancer Res. 38(1): 18. doi: 10.1186/s13046-018-1011-0

Zhu, C.L. & Huang, Q. 2019. Overexpression of the SMYD3 promotes proliferation, migration, and invasion of pancreatic cancer. Dig. Dis. Sci. doi: 10.1007/s10620-019-05797-y

Zhu, C.L. & Huang, Q. 2020. Overexpression of the SMYD3 promotes proliferation, migration, and invasion of pancreatic cancer. Dig. Dis. Sci. 65(2): 489-499. doi: 10.1007/s10620-019-05797-y

Zhu, W., Qian, J., Ma, L., Ma, P., Yang, F. & Shu, Y. 2017. MiR-346 suppresses cell proliferation through SMYD3 dependent approach in hepatocellular carcinoma. Oncotarget 8(39): 65218-65229. doi: 10.18632/oncotarget.18060

Zhu, Y., Zhu, M.X., Zhang, X.D., Xu, X.E., Wu, Z.Y., Liao, L.D., Li, L.Y., Xie, Y.M., Wu, J.Y., Zou, H.Y., Xie, J.J., Li, E.M. & Xu, L.Y. 2016. SMYD3 stimulates EZR and LOXL2 transcription to enhance proliferation, migration, and invasion in esophageal squamous cell carcinoma. Hum. Pathol. 52: 153-163. doi: 10.1016/j.humpath.2016.01.012

Zuo, S.R., Zuo, X.C., He, Y., Fang, W.J., Wang, C.J., Zou, H., Chen, P., Huang, L.F., Huang, L.H., Xiang, H. & Liu, S.K. 2018. Positive expression of SMYD2 is associated with poor prognosis in patients with primary hepatocellular carcinoma. J. Cancer 9(2): 321-330. doi: 10.7150/jca.22218

 

*Corresponding author; email: amnasajjad7@yahoo.com

 

 

 

 

 

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