LINC02154 promotes the proliferation and metastasis of hepatocellular carcinoma by enhancing SPC24 promoter activity and activating the PI3K-AKT signaling pathway

Background Abnormal expression of long non-coding RNAs (lncRNAs) has been associated with the initiation and progression of hepatocellular carcinoma but, as yet, the clinicopathologic significance and potential role of Linc02154 in HCC remains to be determined. Here, we aimed to investigate the potential role and mode of action of Linc02154 in HCC. Methods The expression of Linc02154 in 20 pairs of HCC/normal tissues and 7 HCC cell lines was detected by qRT-PCR. The localization of Linc02154 in HCC cells was detected using fluorescence in situ hybridization and nuclear-plasma separation assays. MTS, EdU incorporation, colony formation, flow cytometry, scratch wound-healing and transwell assays were performed to assess the role of Linc02154 in HCC cell proliferation, migration and invasion in vitro, and BALB/c nude mice xenografts were used to evaluate its role in vivo. RNA sequencing and Western blotting were used to evaluate the regulatory effect of Linc02154 on SPC24 gene expression. A dual-luciferase reporter assay was used to assess a putative interaction of Linc02154 with the SPC24 promoter. Results We identified a new lncRNA, Linc02154, that is highly expressed in HCC cells and tissues of patients with a poor overall survival. Functional experiments revealed that exogenous Linc02154 expression in MHCC-97H and SK-Hepl cells promoted their proliferation, migration and invasion in vitro and their tumorigenesis in vivo. Using a dual luciferase reporter assay we found that Linc02154 can enhance SPC24 promoter (-500 bp similar to-1000 region) activity. Exogenous over-expression of Linc02154 led to up-regulation of SPC24 by activating PI3K/AKT and its downstream signals, including cell cycle progression and EMT-associated gene expression. Conclusion Our data suggest that Linc02154 may serve as a valuable biomarker of HCC and as a potential therapeutic target.

Automated summary

We identified a novel long non-coding RNA, Linc02154, which is highly expressed in hepatocellular carcinoma (HCC) cells and tissues and associated with poor overall survival of patients. Functional experiments demonstrated that exogenous expression of Linc02154 promoted proliferation, migration, invasion, and tumorigenesis of HCC cells both in vitro and in vivo. Mechanistically, Linc02154 enhanced the activity of the SPC24 promoter and up-regulated SPC24 expression through activation of the PI3K/AKT signaling pathway and its downstream targets, including cell cycle progression and EMT-associated gene expression.