Reexpression of Let-7g microRNA inhibits the proliferation and migration via K-Ras/HMGA2/snail axis in hepatocellular carcinoma.
Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressed in vitro in hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability. In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agent in vivo in the treatment of hepatocellular carcinoma at the earlier stage.
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Ke-Ji
KJ
Chen
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Ying
Y
Hou
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Kui
K
Wang
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Jun
J
Li
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Yong
Y
Xia
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Xiao-Yu
XY
Yang
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Gang
G
Lv
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Xiang-Lei
XL
Xing
Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, 225 Changhai Road, Shanghai 200438, China.
Feng
F
Shen
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras); D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D025743:HMGA2 Protein; C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C487931:mirnlet7 microRNA, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins