Institute of Digestive Diseases, Xuzhou Medical University; Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China.
Oncol Rep. 2021 Jan;45(1):73-82. doi: 10.3892/or.2020.7864. Epub 2020 Nov 20.
Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. Long non‑coding RNAs (lncRNAs) have been reported to frequently participate in the carcinogenesis and development of various types of cancer, including HCC. However, the molecular mechanisms of lncRNA ST8SIA6‑AS1 in HCC remain poorly understood. The present study performed bioinformatics analysis, in addition to using reverse transcription‑quantitative PCR (RT‑qPCR), nuclear‑cytoplasmic fractionation, RNA immunoprecipitation, and Transwell, wound healing, and dual‑luciferase reporter assays, to determine the biological role and regulatory mechanisms of ST8SIA6‑AS1 in HCC. The results revealed that the expression levels of ST8SIA6‑AS1 were upregulated in HCC tissues and cell lines, which were associated with a poor prognosis. Moreover, the genetic knockdown of ST8SIA6‑AS1 inhibited the hypoxia‑induced HCC cell migration and invasion. Additionally, microRNA (miR)‑338, which exhibited downregulated expression levels in HCC tissues and cell lines, was discovered to bind with ST8SIA6‑AS1. The inhibition of miR‑338 partially reversed the inhibitory effects of ST8SIA6‑AS1‑knockdown on the migration and invasion of HCC cells under hypoxia. Subsequently, methylphosphate capping enzyme (MEPCE) was identified to be targeted and negatively regulated by miR‑338. Notably, the overexpression of MEPCE recovered the inhibitory influence over the migratory and invasive abilities of hypoxia‑treated HCC cells promoted by ST8SIA6‑AS1 inhibition. In conclusion, the findings of the present study suggest that lncRNA ST8SIA6‑AS1 may promote the migration and invasion of hypoxia‑induced HCC cells via the miR‑338/MEPCE axis, indicating a potential diagnostic or therapeutic marker for HCC treatment.
肝细胞癌（HCC）是全球最常见的癌症类型之一。长链非编码 RNA（lncRNA）已被报道经常参与各种类型癌症的发生和发展，包括 HCC。然而，lncRNA ST8SIA6-AS1 在 HCC 中的分子机制仍知之甚少。本研究进行了生物信息学分析，此外还使用了逆转录-定量 PCR（RT-qPCR）、核-质分离、RNA 免疫沉淀和 Transwell、划痕愈合和双荧光素酶报告基因检测，以确定 ST8SIA6-AS1 在 HCC 中的生物学作用和调控机制。结果显示，ST8SIA6-AS1 在 HCC 组织和细胞系中的表达水平上调，与预后不良相关。此外，ST8SIA6-AS1 的遗传敲低抑制了缺氧诱导的 HCC 细胞迁移和侵袭。此外，miR-338 在 HCC 组织和细胞系中的表达水平下调，被发现与 ST8SIA6-AS1 结合。miR-338 的抑制部分逆转了 ST8SIA6-AS1 敲低对缺氧条件下 HCC 细胞迁移和侵袭的抑制作用。随后，鉴定出甲基磷酸帽酶（MEPCE）是 miR-338 的靶基因，并受其负调控。值得注意的是，MEPCE 的过表达恢复了 ST8SIA6-AS1 抑制对缺氧处理的 HCC 细胞迁移和侵袭能力的抑制作用。综上所述，本研究的结果表明，lncRNA ST8SIA6-AS1 可能通过 miR-338/MEPCE 轴促进缺氧诱导的 HCC 细胞迁移和侵袭，为 HCC 的治疗提供了一个潜在的诊断或治疗标志物。
