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.

中文翻译：

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长链非编码 RNA ZSCAN16-AS1 通过诱骗 microRNA-451a 并因此增加 ATF2 表达来促进肝细胞癌的恶性特性。

长链非编码 RNA (lncRNA) 在肝细胞癌 (HCC) 致癌性中的重要性已被广泛研究。然而，直到本研究之前，很少在 HCC 中探索 ZSCAN16 反义 RNA 1 (ZSCAN16-AS1) 的详细功能。在本研究中，进行了实验以阐明 ZSCAN16-AS1 是否与 HCC 的发生和进展有关，并探索可能的潜在机制。使用逆转录定量 PCR 分析 ZSCAN16-AS1 表达。ZSCAN16-AS1对HCC细胞生物学行为的影响通过功能实验得到证实。ZSCAN16-AS1 与 microRNA-451a (miR-451a) 的直接结合能力通过荧光素酶报告基因测定和 RNA 免疫沉淀来显示。癌症基因组图谱数据库和本研究的队列证实了 ZSCAN16-AS1 在 HCC 中的高表达。生存数据显示，与 ZSCAN16-AS1 水平低的患者相比，ZSCAN16-AS1 水平高的患者预后更差。ZSCAN16-AS1敲低后，HCC细胞增殖、迁移和侵袭得到抑制，而细胞凋亡得到促进体外。ZSCAN16-AS1 的缺失限制了体内 HCC 细胞的肿瘤生长. 从机制上讲，ZSCAN16-AS1 通过诱骗 HCC 细胞中的 miR-451a 充当竞争性内源性 RNA。此外，激活转录因子 2 (ATF2) 是 miR-451a 的直接靶标，受 ZSCAN16-AS1 的调节，其通过隔离 miR-451a 发挥作用。此外，miR-451a 敲低或 ATF2 恢复逆转了由 ZSCAN16-AS1 沉默引发的增殖抑制、细胞凋亡促进以及迁移和侵袭抑制。总之，ZSCAN16-AS1 是一种促癌基因 lncRNA，通过控制 miR-451a/ATF2 轴加重了 HCC 的恶性程度。了解 HCC 中 ZSCAN16-AS1/miR-451a/ATF2 的竞争性内源性 RNA 网络可能有助于开发有吸引力的分子治疗靶点。