title: MiR-302c inhibits tumor growth of hepatocellular carcinoma by suppressing the endothelial-mesenchymal transition of endothelial cells.
abstract: Endothelial cells (ECs) are critical for angiogenesis, and microRNA plays important roles in this process. In this study, we investigated the function and mechanism of miR-302c in the process of endothelial-mesenchymal transition (EndMT) in ECs. When miR-302c was overexpressed in HUVECs, the motility of the HUVECs was weakened; the expression levels of EndMT markers were also changed: vascular endothelial (VE)-cadherin was up-regulated, whereas β-catenin, FSP1, and α-SMA were down-regulated. Further in vivo and in vitro experiments showed that the growth of HCC was inhibited when co-cultured or co-injected with HUVECs overexpressing miR-302c. On the contrary, when miR-302c was suppressed in HUVECs, the opposite results were observed. Reporter assays showed that miR-302c inhibited metadherin (MTDH) expression through directly binding to its 3'UTR. In addition, compared to ECs isolated from normal liver tissues of HCC patients, ECs isolated from tumor tissues expressed markedly low levels of miR-302c but high levels of MTDH. These results suggest that EC-specific miR-302c suppresses tumor growth in HCC through MTDH-mediated inhibition of EndMT. MTDH and miR-302c might provide a new strategy for anti-angiogenic therapy in HCC.
authors.affiliation: 1] Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education [2].
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.affiliation: 1] Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education [2].
authors.forename: Qi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: 1] Department of Gynecology, Obstetrics and Gynecology Hospital, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Fudan University, Shanghai 200032, China [2].
authors.forename: Luo-Qi
authors.initials: LQ
authors.lastname: Jia
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education.
authors.forename: Ai-Wu
authors.initials: AW
authors.lastname: Ke
authors.affiliation: Department of Pathology, Zhong Shan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zeng
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education.
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.affiliation: Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: 1] Liver Cancer Institute, Zhong Shan Hospital, Fudan University, Shanghai, 200032 China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education [2] Shanghai Key Laboratory of Organ Transplantation, Zhong Shan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D034622:RNA Interference; D016601:RNA-Binding Proteins; D047368:Tumor Burden
chemical_list: D015815:Cell Adhesion Molecules; C532169:MIRN302A microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins