MiR-612 suppresses the stemness of liver cancer via Wnt/β-catenin signaling.
Previous research showed that microRNA-612 (miR-612) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of hepatocellular carcinoma (HCC). AKT2 was confirmed to be a direct target of miR-612, through which the epithelial-mesenchymal transition (EMT) and metastasis of HCC were inhibited. Our present findings reveal that miR-612 is able to suppress the stemness of HCC by reducing the number and size of tumorspheres as well as clone formation in soft agar, and to relieve drug resistance to cisplatin and 5-fluorouracil. In addition, miR-612 hampered the capacity of tumorigenesis in NOD/SCID mice and redistributed the tumor invasive frontier of miR-612-modulating cells. Finally, our findings suggest that Wnt/β-catenin signaling is required in the regulation of EMT-associated stem cell-like traits by miR-612.
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Jun
J
Tang
Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Zhong-Hua
ZH
Tao
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Duo
D
Wen
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Jin-Liang
JL
Wan
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Dong-Li
DL
Liu
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Shu
S
Zhang
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Jie-Feng
JF
Cui
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Hui-Chuan
HC
Sun
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Lu
L
Wang
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Institute of Biomedical Sciences of Fudan University, Shanghai 200032, China.
Jian
J
Zhou
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China; Institute of Biomedical Sciences of Fudan University, Shanghai 200032, China.
Jia
J
Fan
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China. Electronic address: wu.weizhong@zs-hospital.sh.cn.
Wei-Zhong
WZ
Wu
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000187:drug effects / Q000502:physiology
C582274:MIRN612 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin; D002945:Cisplatin; D005472:Fluorouracil
Cancer stem cells; Hepatocellular carcinoma; Invasive frontier; Wnt/β-catenin; miR-612