Decreased expression of long non-coding RNA GAS5 indicates a poor prognosis and promotes cell proliferation and invasion in hepatocellular carcinoma by regulating vimentin.
Decreased expression of long non-coding RNA GAS5 indicates a poor prognosis and promotes cell proliferation and invasion in hepatocellular carcinoma by regulating vimentin.
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长链非编码RNA GAS5表达降低提示预后不良，并通过调节波形蛋白促进肝细胞癌细胞增殖和侵袭。
DOI：
10.3892/mmr.2015.4716
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发表时间：
2016-02
影响因子：
3.4
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Chang L;Li C;Lan T;Wu L;Yuan Y;Liu Q;Liu Z
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。近年来的研究表明，长链非编码rna （long non-coding RNAs, lncRNAs）在癌变过程中起着关键作用。本研究旨在探讨lncRNA GAS5在HCC组织中的作用，并明确生长抑制特异性5 （growth arrest-specific 5, GAS5）在肝癌细胞增殖、侵袭和凋亡调控中的作用。采用定量聚合酶链反应和原位杂交技术对50例肝癌患者肿瘤组织及相应癌旁组织中GAS5的表达进行了研究。GAS5低表达与肿瘤分化（P<0.010）及门静脉肿瘤血栓形成（P=0.001）显著相关。多因素分析显示GAS5表达是总生存率的独立预测因子（P=0.017）。进一步实验表明，过表达GAS5可显著抑制肝癌细胞的体外增殖和侵袭。过表达GAS5可显著促进肝癌细胞凋亡。此外，在体外和体内均证实GAS5负调控vimentin的表达。值得注意的是，vimentin敲低促进gas5 - pcdna3.1抑制肝癌细胞增殖。总之，本研究提示GAS5在HCC分子病因学中的重要作用，并提示GAS5在HCC治疗中的潜在应用。
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are key in carcinogenesis. The aim of the present study was to investigate the role of lncRNA GAS5 in HCC tissues and to define the role of growth arrest-specific 5 (GAS5) in the regulation of hepatoma cell proliferation, invasion and apoptosis. Quantitative polymerase chain reaction and in situ hybridization were performed to investigate the expression of GAS5 in tumor tissues and corresponding adjacent tissues from 50 patients with HCC. Low expression of GAS5 was significantly correlated with differentiation (P<0.010) and portal vein tumor thrombosis (P=0.001). Multivariate analysis indicated that GAS5 expression was an independent predictor for overall survival (P=0.017). Further experiments demonstrated that overexpression of GAS5 significantly suppressed the proliferation and invasion of hepatoma cells in vitro. Overexpression of GAS5 significantly promoted the apoptosis of hepatoma cells. In addition, it was demonstrated that GAS5 negatively regulates vimentin expression in vitro and in vivo. Notably, vimentin knockdown promoted GAS5-pcDNA3.1-inhibition of hepatoma cell proliferation. In conclusion, the present study suggests an important role of GAS5 in the molecular etiology of HCC and suggests the potential application of GAS5 in HCC therapy.