Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-IκB

被引:94
作者
Fang, Luo [1 ]
Sun, Jiao [1 ]
Pan, Zongfu [1 ]
Song, Yu [1 ]
Zhong, Like [1 ]
Zhang, Yiwen [1 ]
Liu, Yujia [1 ]
Zheng, Xiaowei [1 ]
Huang, Ping [1 ]
机构
[1] Zhejiang Canc Hosp, Dept Pharm, 1 E Banshan Rd, Hangzhou 310022, Zhejiang, Peoples R China
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2017年 / 313卷 / 02期
基金
中国国家自然科学基金;
关键词
long non-coding RNA nuclear-enriched abundant transcript 1; hepatocellular carcinoma; microRNA-129-5p; valosin-containing protein; I kappa B; CANCER PROGRESSION; GASTRIC-CANCER; MIR-129-5P; EXPRESSION; MIGRATION; LNCRNAS; AXIS; LUNG;
D O I
10.1152/ajpgi.00426.2016
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. NEAT1 and microRNA (miR)-129-5p expression in HCC tissues and cell lines was quantified by means of quantitative PCR. The effects of NEAT1 expression inhibition or upregulation in HCC cell lines were analyzed in terms of cell viability and apoptosis. Biological software was used to predict the binding sites of NEAT1 and miR-129-5p. The expression of the miR-129-5p target molecules valosin-containing protein (VCP) and I kappa B was detected using Western blotting. The effect of NEAT1 on tumor growth was observed in mouse models of transplanted hepatoma. In the present study, it was concluded that the expression of NEAT1 was significantly increased in the HCC tissues and cell lines. Meanwhile, after downregulating NEAT1 expression in HepG2/Huh7 cell lines, the cell viability was significantly lowered, whereas the corresponding rate of apoptosis was significantly increased. Additionally, it was found that the NEAT1 and miR-129-5p expression showed a negative correlation in HCC tissues. It was further proved that there was a certain negative regulatory mechanism between NEAT1 and miR-129-5p, which was related to the expression of VCP and I kappa B. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited tumor growth. The study concluded that the overexpression of NEAT1 inhibited the expression of miR-129-5p by regulating VCP/I kappa B, thereby promoting the proliferation of HCC cells. This study provides new insights into the pathogenesis of HCC, as well as identifying new target genes for diagnosis and treatment. NEW & NOTEWORTHY The results provide strong evidence that upregulated NEAT1 promotes the proliferation of cancer cells in hepatocellular carcinoma (HCC) and this regulatory mechanism depends on the microRNA (miR)-129-5p-valosin-containing protein-I kappa B axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC.
引用
收藏
页码:G150 / G156
页数:7
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