RRC ID 64583
著者 El-Mezayen H, Yamamura K, Yusa T, Nakao Y, Uemura N, Kitamura F, Itoyama R, Yamao T, Higashi T, Hayashi H, Imai K, Chikamoto A, Yamashita YI, Baba H.
タイトル MicroRNA-25 Exerts an Oncogenic Function by Regulating the Ubiquitin Ligase Fbxw7 in Hepatocellular Carcinoma.
ジャーナル Ann Surg Oncol
Abstract BACKGROUND:MicroRNA (miRNA) expression abnormalities are implicated in tumor progression. Previous reports have indicated that microRNA-25 (miR-25) acts as a tumor suppressor or oncogene in diverse cancers. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are still unclear. F-box and WD repeat domain 7 (Fbxw7) is a critical tumor suppressor and is one of the most important deregulated proteins of the ubiquitin-proteasome system in cancer. Our objective was to elucidate the role of miR-25 and Fbxw7 in HCC and to clarify the mechanism by which Fbxw7 is regulated.
METHODS:Fbxw7 expression was estimated in 210 fixed paraffin-embedded HCC samples by immunohistochemistry, and miR-25 expression was evaluated in 142 frozen HCC tissue samples by quantitative real-time PCR. Oncogenic functions of miR-25 and its role in the regulation of Fbxw7 expression were assayed in vitro.
RESULTS:miR-25 was overexpressed in HCC tissue compared with adjacent normal tissue and significantly correlated with a poorer prognosis. Moreover, it was inversely correlated with Fbxw7 expression in HCC tissues. Furthermore, miR-25 inhibition significantly reduced the proliferation, migration, and invasion of HCC cells in vitro.
CONCLUSION:miR-25 may promote tumor progression in HCC patients by repression of Fbxw7 and could serve as a promising molecular target for HCC treatment.
巻・号 28(12)
ページ 7973-7982
公開日 2021-11-1
DOI 10.1245/s10434-021-09778-2
PII 10.1245/s10434-021-09778-2
PMID 33886022
MeSH Carcinoma, Hepatocellular* / genetics Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line, Tumor Cell Proliferation F-Box-WD Repeat-Containing Protein 7* / genetics Gene Expression Regulation, Neoplastic Humans Liver Neoplasms* / genetics MicroRNAs* / genetics Oncogenes Prognosis Ubiquitin-Protein Ligases / genetics
IF 4.061
リソース情報
ヒト・動物細胞 HuH-7(RCB1366) Li-7(RCB1941) Hep G2(RCB1648)