Inhibition of hepatocelluar carcinoma MAT2A and MAT2beta gene expressions by single and dual small interfering RNA.
RNA interference (RNAi) has been successfully applied in suppression of hepatic cancer genes. In hepatocelluar carcinoma cell, one methionine adenosyltransferase (MAT) isozyme, MATII was found to have two catalytic subunits which were encoded by MAT2A and MAT2beta respectively. During tumorigeness of hepatocelluar carcinoma, expressions of the two genes were discovered to be increased combining with a switch of MAT (form MATI to MATII), To figure out the role played by MATII in hepatic cancer, In this study, for the first time we established a dual small interfering RNA (siRNA) expression system, which could simultaneously express two different siRNA molecules specifically targeting two genes. To test the effectiveness of this system, we applied this approach to express simultaneously two different siRNA duplexes that specifically target MAT2A and MAT2beta genes of hepatocelluar carcinoma respectively in HepG2 cell. Results indicated that dual siRNA could simultaneously inhibit the expression of MAT2A and MAT2beta gene by 89.5% and 97.8% respectively, In addition, dual siRNA molecules were able to significantly suppress growth of hepatocelluar carcinoma cell in vitro as well as induce apoptosis which was involved in arrest cell cycle at the G1/S checkpoint and the expressions of p21, p27 and Bax.
Wang
Qun
Q
Department of General Surgery, Zhongnan Hospital of Wuhan University, Hubei Province, PR China. swander@126.com
Liu
Quan-yan
QY
Liu
Zhi-Su
ZS
Qian
Qun
Q
Sun
Quan
Q
Pan
Ding-yu
DY
D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008716:Methionine Adenosyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; C527161:MAT2A protein, human; C527162:MAT2B protein, human; D008716:Methionine Adenosyltransferase