Sains Malaysiana 42(8)(2013): 1131–1137


Targeted RNAi of the Mitogen-activated Protein Kinase Pathway Genes in

Acute Myeloid Leukemia Cells

(RNAi Sasar Gen Tapak Jalan Protein Kinase Diaktifkan-Mitogen dalam Mieloid Leukemia Akut)



M.R. Mohd Hafiz1*, M.Z. Mazatulikhma2, F.A. Mohd Faiz1 & M.S. Mohamed Saifulaman1


1Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor



2Institute of Science, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia



Received: 2 April 2012/Accepted: 16 December 2012



In this study, RNA interference (RNAi) was carried out as an experimental technique to knockdown three mitogen-activated protein kinase (MAPK) pathway genes, raf-1, mekk1 and mlk3 in acute myeloid leukemia (AML) cells. Conventionally, RNAi knockdown experiments target a single gene for functional studies or therapeutic purposes. We wanted to explore the potential differences or similarities between targeting single targets or multiple target genes in a single application. We achieved knockdown of gene expression levels of between 40 and 60% for the RNAi experiments, with better knockdown observed in single target gene experiments in comparison with the multiple target gene experiment. Microarray analysis indicated that the transfection process had most likely induced the immune response from the cells in every RNAi treatment. This might indicate that when the MAPK signaling pathway is partially blocked, in tandem with the immune response, the cells will begin signaling for apoptosis leading to cellular death of the leukemic cells.


Keywords: Acute myeloid leukemia; immune response; MAPK pathway; RNA interference



Dalam kajian ini, penggangguan RNA (RNAi) digunakan sebagai teknik uji kaji untuk menurunkan tiga gen protein kinase diaktifkan-mitogen (MAPK) iaitu gen raf1, mekk1 dan mlk3 di dalam sel mieloid leukemia akut (AML). Kebiasaannya, eksperimen RNAi dijalankan untuk menyasar satu gen sahaja demi mengkaji fungsi atau peranan terapi. Kami telah mengkaji potensi perbezaan atau persamaan antara menyasar satu atau lebih gen dalam satu aplikasi. Kami berjaya mencapai penurunan pengekspresan gen daripada 40% hingga 60% dan RNAi kelihatan lebih berkesan melalui penyasaran satu gen. Analisis mikroatur menunjukkan bahawa proses transfeksi kemungkinan tinggi telah mengaruh tindak balas imun dalam setiap perlakuan RNAi yang telah dilakukan. Ini mungkin memberi petunjuk bahawa apabila pengisyaratan tapak jalan MAPK dihalang separa, disertakan pengaruhan tindak balas imun, tapak laluan apoptosis akan dimulakan dan mengakibatkan kematian sel kepada sel-sel leukemia.


Kata kunci: Mieloid leukemia akut; penggangguan RNA; tapak jalan MAPK; tindak balas imun


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