STAT1‐induced upregulation of lncRNA RHPN1‐AS1 predicts a poor prognosis of hepatocellular carcinoma and contributes to tumor progression via the miR‐485/CDCA5 axis

基因敲除 长非编码RNA 肝细胞癌 癌症研究 下调和上调 生物标志物 反义RNA 转移 肿瘤进展 生物 小RNA 竞争性内源性RNA 细胞生长 调节器 癌症 细胞凋亡 核糖核酸 基因 遗传学
作者
Xiaozhan Zhang,Zhenzhen Yan,Lei Wang,Shijie Zhang,Ming Gao
出处
期刊:Journal of Cellular Biochemistry [Wiley]
卷期号:121 (12): 4741-4755 被引量:20
标识
DOI:10.1002/jcb.29689
摘要

Abstract Long noncoding RNAs (lncRNAs) act as a critical regulator in tumor progression, but few lncRNAs have been functionally characterized in hepatocellular carcinoma (HCC). Using The Cancer Genome Atlas datasets and bioinformatic technology, we screened and identified a novel HCC‐related lncRNA, RHPN1 antisense RNA 1 (RHPN1‐AS1). We found that the levels of RHPN1‐AS1 were distinctly upregulated in both HCC tissues and cell lines. RHPN1‐AS1 was activated by the transcription factor STAT1. Clinical investigations suggested that higher levels of RHPN1‐AS1 were distinctly correlated with histologic grade, advanced tumor, node, metastasis stage, and poorer clinical prognosis. Multivariate assays identified high RHPN1‐AS1 expression as an unfavorable prognostic biomarker for patients with HCC. Functional study revealed that knockdown of RHPN1‐AS1 was able to suppress cells proliferation and metastasis, and promote cell apoptosis. Further mechanistic investigation suggested that RHPN1‐AS1 could promote CDCA5 expressions by functioning as a competing endogenous RNA for miR‐485. This interaction resulted in consequentially suppression of HCC cells proliferation, migration, and invasion. Our findings for the first time illustrate how RHPN1‐AS1 displayed its tumor‐promotive roles in HCC and may offer a new biomarker and a potential therapeutic target for patients with HCC.
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