Long non-coding RNA ZSCAN16-AS1 promotes the malignant properties of hepatocellular carcinoma by decoying microRNA-451a and consequently increasing ATF2 expression

The importance of long noncoding RNAs (lncRNAs) in the oncogenicity of hepatocellular carcinoma (HCC) has been widely studied. However, the detailed functions of ZSCAN16 antisense RNA 1 (ZSCAN16-AS1) have seldom been explored in HCC until the present study. In the present study, experiments were performed to clarify whether ZSCAN16-AS1 is implicated in the oncogenesis and progression of HCC and to explore the possible underlying mechanisms. ZSCAN16-AS1 expression was analyzed using reverse transcription-quantitative PCR. The effects of ZSCAN16-AS1 on the biological behavior of HCC cells were demonstrated by functional experiments. The direct binding capacity of ZSCAN16-AS1 with microRNA-451a (miR-451a) was indicated by the luciferase reporter assay and RNA immunoprecipitation. The high expression of ZSCAN16-AS1 was confirmed in HCC by The Cancer Genome Atlas database and the cohort of the present study. Survival data revealed that patients with a high ZSCAN16-AS1 level had worse prognosis compared with those with a low ZSCAN16-AS1 level. Following ZSCAN16-AS1 knockdown, HCC cell proliferation, migration and invasion were curbed, whereas cell apoptosis was promoted in vitro. The absence of ZSCAN16-AS1 restricted tumor growth of HCC cells in vivo. Mechanistically, ZSCAN16-AS1 acted as a competing endogenous RNA by decoying miR-451a in HCC cells. Furthermore, activating transcription factor 2 (ATF2), a direct target of miR-451a, was under the regulation of ZSCAN16-AS1, which was exerted by sequestering miR-451a. In addition, miR-451a knockdown or ATF2 resumption reversed the proliferation suppression, apoptosis promotion and migration and invasion inhibition triggered by ZSCAN16-AS1 silencing. In conclusion, ZSCAN16-AS1, a pro-oncogenic lncRNA, aggravated the malignancy of HCC by controlling the miR-451a/ATF2 axis. An understanding of the competing endogenous RNA network of ZSCAN16-AS1/miR-451a/ATF2 in HCC might be instrumental in the development of attractive targets for molecular therapy.