MicroRNA-25 Exerts an Oncogenic Function by Regulating the Ubiquitin Ligase Fbxw7 in Hepatocellular Carcinoma

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...

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Bibliographic Details
Published in:Annals of surgical oncology 2021-11, Vol.28 (12), p.7973-7982
Main Authors: El-mezayen, Hatem, Yamamura, Kensuke, Yusa, Toshihiko, Nakao, Yosuke, Uemura, Norio, Kitamura, Fumimasa, Itoyama, Rumi, Yamao, Takanobu, Higashi, Takaaki, Hayashi, Hiromitsu, Imai, Katsunori, Chikamoto, Akira, Yamashita, Yo-ichi, Baba, Hideo
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - genetics
Cdc4 protein
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
Hepatocellular carcinoma
Humans
Immunohistochemistry
Liver cancer
Liver Neoplasms - genetics
Medicine
Medicine & Public Health
MicroRNAs
MicroRNAs - genetics
miRNA
Molecular modelling
Oncogenes
Oncology
Paraffin
Prognosis
Proteasomes
Surgery
Surgical Oncology
Translational Research
Tumor suppressor genes
Ubiquitin
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
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Summary: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.
ISSN:1068-9265
1534-4681
DOI:10.1245/s10434-021-09778-2