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.

WW domain binding protein 2 (WBP2) as an oncogene in breast cancer: mechanisms and therapeutic prospects—a narrative review

“…This is the only study to verify that circRNAs are involved in the regulation of WBP2 so far. to promote HCC progression (45,46); and so on. These findings are potential directions for lncRNA' involvement in WBP2 regulation.…”

Association of FOXO3 Expression with Tumor Pathogenesis, Prognosis and Clinicopathological Features in Hepatocellular Carcinoma: A Systematic Review with Meta-Analysis

“…Interestingly, Lu et al [ 29 ] evidenced that FOXO3 is highly expressed and overactivated in HCC patients, which was associated with strong liver damage and overexpression of HCC-related genes, suggesting that FOXO3 overexpression is involved in tumorigenesis promotion. Additional reports from pre-clinical studies also indicated that FOXO3 upregulation is related to HCC oncogenicity via the overexpression of the long noncoding RNAs (lncRNAs) PRR34 antisense RNA 1 (PRR34-AS1) [ 17 ] and LOC554202 [ 30 ], or by the circular RNA circFBXO11/miR-605 axis [ 13 ]. Contrary to all the above-mentioned results, the article by Wu et al [ 31 ] described that reduction in FOXO3 nuclear translocation and activity could be involved in sepiapterin reductase-mediated HCC progression.…”

Role of LncRNAs in the Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

“…Since the EMT process involves gene expression and modification, as well as transcription regulation, experts and scholars worldwide are devoting increasing attention to the role of lncRNAs as important regulatory factors in this process. LncRNAs ultimately enhance ( 34 , 35 ) or inhibit ( 27 , 36 ) the EMT process by directly or indirectly targeting EMT-TFs or EMT markers. As mentioned above, there are five functional categories of lncRNAs, and the most typical category observed in EMT is RNA sponges or competitive endogenous RNA (ceRNA) ( Table 1 ), which can competitively bind with miRNAs and upregulate the expression of target genes to regulate EMT.…”