Department of Hepatobiliary and Pancreatic Surgery, Ningbo First Hospital, Zhejiang, Ningbo 315010, China.
Biomed Res Int. 2019 Jan 13;2019:2973289. doi: 10.1155/2019/2973289. eCollection 2019.
Long noncoding RNA (LncRNA) growth arrest-specific 5 (GAS5) has been characterized as a tumor suppressor in numerous kinds of human cancers. Its anticancer function in hepatocellular carcinoma (HCC) includes repression of cell proliferation and metastasis, leaving the internal mechanisms unclear. In this study, we intended to examine the anti-invasion effects of GAS5 on HCC and explore the downstream regulatory mechanisms.
Expression of GAS5 and microRNA-135b (miR-135b) was analyzed by qRT-PCR in paired HCC tissue samples. Their correlation with HCC patients' survival was determined. Transwell assays were done to evaluate invasion ability. Targeting of GAS5 and RECK by miR-135b was confirmed by qRT-PCR, western blot, and luciferase reporter assays.
Decreased GAS5 and increased miR-135b in HCC inversely correlate with each other and both correlate with poor prognosis of HCC patients. Functionally, GAS5 suppresses while miR-135b promotes HCC cell invasion capacities . Mechanistically, GAS5 is a target of miR-135b. Furthermore, GAS5 positively regulates expression of RECK, also a target of miR-135b, which further inhibits MMP-2 expression and contributes to invasion repression.
GAS5 acted as a tumor suppressor in HCC invasion in a competing endogenous RNA manner. Our findings indicate that GAS5 is a promising therapeutic target for HCC treatment.
长链非编码 RNA（lncRNA）生长停滞特异性基因 5（GAS5）已被鉴定为多种人类癌症的肿瘤抑制因子。其在肝细胞癌（HCC）中的抗癌功能包括抑制细胞增殖和转移，但其内在机制尚不清楚。在这项研究中，我们旨在研究 GAS5 对 HCC 的抗侵袭作用，并探讨下游调控机制。
通过 qRT-PCR 分析配对 HCC 组织样本中 GAS5 和 microRNA-135b（miR-135b）的表达。确定它们与 HCC 患者生存的相关性。通过 Transwell 分析评估侵袭能力。通过 qRT-PCR、western blot 和荧光素酶报告实验证实 GAS5 和 RECK 被 miR-135b 靶向。
GAS5 在 HCC 中的表达降低，miR-135b 表达增加，两者呈负相关，且均与 HCC 患者的预后不良相关。功能上，GAS5 抑制 HCC 细胞侵袭能力，而 miR-135b 促进 HCC 细胞侵袭能力。机制上，GAS5 是 miR-135b 的靶基因。此外，GAS5 正向调节 miR-135b 的靶基因 RECK 的表达，进一步抑制 MMP-2 的表达，从而抑制侵袭。
GAS5 通过竞争性内源性 RNA 方式在 HCC 侵袭中发挥肿瘤抑制作用。我们的研究结果表明，GAS5 是治疗 HCC 的有前途的治疗靶点。
