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长链非编码 RNA SOX21-AS1 与肝细胞癌的进展相关,并通过表观遗传沉默 p21 来预测预后。

LncRNA SOX21-AS1 is associated with progression of hepatocellular carcinoma and predicts prognosis through epigenetically silencing p21.

机构信息

Department of Radiology, Qilu Hospital, Shandong University, Jinan, 250012, China.

Department of Anesthesiology, Yidu Central Hospital, Weifang Medical University, Qingzhou, 262500, China.

出版信息

Biomed Pharmacother. 2018 Aug;104:137-144. doi: 10.1016/j.biopha.2018.05.010. Epub 2018 May 14.

Abstract

Long non-coding RNAs (lncRNAs) have been widely reported in various cancers due to their special molecular mechanisms. LncRNA SOX21-AS1 has been discovered to be a tumor facilitator in several types of human cancers. However, the expression pattern, clinical value and biological effects in hepatocellular carcinoma (HCC) are still unknown. In this study, we detected the high expression level of SOX21-AS1 in tumor tissues and cell lines through performing qRT-PCR analysis. The prognostic value of SOX21-AS1 was identified. Moreover, the biological effects of SOX21-AS1 on HCC cell activities were evaluated by functional assays, such as MTT, colony formation assay and transwell assay. As a result, silenced SOX21-AS1 suppressed cell proliferation and metastasis, resulted in cell cycle arrest, and induced apoptosis in hepatocellular carcinoma. Mechanically, RIP was conducted to prove that SOX21-AS1 could bind with EZH2. ChIp assay was carried out and manifested that SOX21-AS1 epigenetically silenced p21 via recruiting EZH2 to the promoter of p21. Finally, rescue assays were designed and carefully conducted to investigate whether SOX21-AS1 can interact with p21 to affect hepatocellular carcinoma progression. Generally, our results suggested that SOX21-AS1 could be a potential prognostic biomarker or a therapeutic target for hepatocellular carcinoma.

摘要

长链非编码 RNA(lncRNA)由于其特殊的分子机制,在各种癌症中得到了广泛的报道。已经发现 lncRNA SOX21-AS1 在几种类型的人类癌症中是一种肿瘤促进因子。然而,其在肝细胞癌(HCC)中的表达模式、临床价值和生物学效应仍不清楚。在这项研究中,我们通过 qRT-PCR 分析检测到肿瘤组织和细胞系中 SOX21-AS1 的高表达水平。确定了 SOX21-AS1 的预后价值。此外,通过 MTT、集落形成实验和 Transwell 实验等功能实验评估了 SOX21-AS1 对 HCC 细胞活性的生物学影响。结果表明,沉默 SOX21-AS1 抑制了细胞增殖和转移,导致细胞周期停滞,并诱导了肝癌细胞凋亡。通过 RIP 证实 SOX21-AS1 可以与 EZH2 结合。进行 ChIP 实验表明,SOX21-AS1 通过招募 EZH2 到 p21 的启动子,表观遗传地下调 p21。最后,设计并仔细进行了挽救实验,以研究 SOX21-AS1 是否可以与 p21 相互作用影响肝细胞癌的进展。总的来说,我们的研究结果表明,SOX21-AS1 可能是肝细胞癌的一个潜在的预后生物标志物或治疗靶点。

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