Silencing of Long Non-coding RNA TTN-AS1 Inhibits Hepatocellular Carcinoma Progression by the MicroRNA-134/ITGB1 Axis

Dig Dis Sci. 2021 Jan 2. doi: 10.1007/s10620-020-06737-x. Online ahead of print.

Abstract

Background: Hepatocellular carcinoma (HCC) causes considerable mortality worldwide. Long non-coding RNA (lncRNA) TTN-AS1 has been recently identified as an oncogene in several cancers, but its role in HCC and the molecules remain largely unknown.

Aims: The study aims to probe the function of lncRNA TTN-AS1 in HCC progression and the molecules involved.

Methods: Differentially expressed lncRNAs between HCC and the adjacent normal tissues were analyzed using a microarray. TTN-AS1 expression in HCC and normal tissues and cells was determined. Targeting relationships between TTN-AS1 and miR-134 and between miR-134 and ITGB1 were validated. Artificial up-regulation or down-regulation of TTN-AS1, miR-134 and ITGB1 was introduced in HCC cells to probe their effects on the biological behaviors of HCC cells. Xenograft tumors were induced in nude mice for in vivo experiments.

Results: TTN-AS1 and ITGB1 were highly expressed, while miR-134 was poorly expressed in HCC tissues. TTN-AS1 enforced ITGB1 expression through sequestering miR-134. Silencing of TTN-AS1 or over-expression of miR-134 inhibited proliferation, invasion, migration, and resistance to death of Huh7 cells. Following miR-134 silencing, further down-regulation of ITGB1 suppressed the malignant behaviors of HUH7 cells. The similar results were reproduced in vivo.

Conclusion: The current study provided evidence that TTN-AS1 might promote HCC progression through sponging miR-134 and the following ITGB1 up-regulation. TTN-AS1 may serve as a potential target for HCC treatment.

Keywords: Competing endogenous RNA; Hepatocellular carcinoma; ITGB1; Long non-coding RNA; MicroRNA-134; Proliferation.