FOXO3诱导的lncRNA LOC554202通过miR-485-5p/BSG轴参与肝细胞癌的进展
FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis
原文发布日期：2021-03-02
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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.
长链非编码RNA（LncRNA）在肝细胞癌（HCC）的恶性行为中扮演重要角色。LncRNA LOC554202作为新近发现的肿瘤相关非编码RNA，其在HCC中的表达与功能尚不明确。本研究首次发现LOC554202在HCC临床样本和细胞系中表达显著上调。临床分析表明，LOC554202的高表达对HCC患者具有诊断价值，且与晚期病程和不良预后呈正相关。进一步研究发现，叉头框蛋白O3（FOXO3）可直接结合LOC554202启动子区域并激活其转录功能。在机制层面，LOC554202通过竞争性结合miR-485-5p，消除该miRNA对其靶基因basigin（BSG）的抑制作用，最终促进HCC转移、上皮间质转化（EMT）及多西他赛化疗耐药。本研究揭示FOXO3诱导的LOC554202通过miR-485-5p/BSG信号轴驱动HCC进展的分子机制，表明调控FOXO3/LOC554202/miR-485-5p/BSG信号通路可能为HCC治疗提供新策略。
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