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FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis.

Abstract
Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). LncRNA LOC554202 (LOC554202) was a newly identified tumor-related lncRNA. However, its expression and function in HCC remained unknown. In this study, we firstly reported that LOC554202 expression was distinctly upregulated in HCC specimens and cell lines. Clinical assays indicated that increased LOC554202 expression had a diagnostic value for HCC patients and was positively associated with advanced stages and poor clinical prognosis. Additionally, forkhead box O3(FOXO3) could bind directly to the LOC554202 promoter region and activate its transcription. Functionally, we observed that knockdown of LOC554202 suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) progress of HCC cells, and promoted apoptosis. Mechanistically, LOC554202 competitively bound to miR-485-5p and prevented the suppressive effects of miR-485-5p on its target gene basigin (BSG), which finally led to HCC metastasis, EMT, and docetaxel chemoresistance. Our data demonstrated that FOXO3-induced LOC554202 contributed to HCC progression by upregulating BSG via competitively binding to miR-485-5p, which suggested that the regulation of the FOXO3/LOC554202/miR-485-5p/BSG axis may have beneficial effects in the treatment of HCC.
AuthorsLin Yang, Wan-Li Deng, Bao-Guo Zhao, Yao Xu, Xiao-Wen Wang, Yu Fang, Hai-Juan Xiao
JournalCancer gene therapy (Cancer Gene Ther) Vol. 29 Issue 3-4 Pg. 326-340 (03 2022) ISSN: 1476-5500 [Electronic] England
PMID33654226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.
Chemical References
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN485 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Basigin
Topics
  • Basigin (genetics, metabolism)
  • Carcinoma, Hepatocellular (pathology)
  • Cell Line, Tumor
  • Cell Movement (genetics)
  • Cell Proliferation (genetics)
  • Forkhead Box Protein O3 (genetics, metabolism)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms (metabolism)
  • MicroRNAs (genetics, metabolism)
  • RNA, Long Noncoding (genetics, metabolism)

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