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.

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.