title: miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma.
abstract: Emerging evidence suggests that microRNAs (miRNAs) play important roles in regulating HCC development and progression; however, the mechanisms by which their specific functions and mechanisms remained to be further explored. miR-129 has been reported in gastric cancers, lung cancer and colon cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in HCC. We also found the downregulation of miR-129 occurred in nearly 3/4 of the tumors examined (56/76) compared with adjacent nontumorous tissues, which was more importantly, correlated to the advanced stage and vascular invasion. We then demonstrated that miR-129 overexpression attenuated HCC cells proliferation and invasion, inducing apoptosis in vitro. Moreover, we used miR-129 antagonist and found that anti-miR-129 promoted HCC cells malignant phenotypes. Mechanistically, our further investigations revealed that miR-129 suppressed cell proliferation and invasion by targeting the 3'-untranslated region of PAK5, as well as miR-129 silencing up-regulated PAK5 expression. Moreover, miR-129 expression was inversely correlated with PAK5 expression in 76 cases of HCC samples. RNA interference of PAK5 attenuated anti-miR-129 mediated cell proliferation and invasion in HCC cells. Taken together, these results demonstrated that miR-129 suppressed tumorigenesis and progression by directly targeting PAK5, defining miR-129 as a potential treatment target for HCC.
authors.affiliation: Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhai
authors.affiliation: Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. Electronic address: drquzengqiang@163.com.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. Electronic address: wudongstc@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001665:Binding Sites; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C541915:Mirn129 microRNA, human; D034741:RNA, Small Interfering; C443802:PAK5 protein, human; D054462:p21-Activated Kinases
keywords: Hepatocellular carcinoma; Invasion; PAK5; Proliferation; miR-129