Fang Luo, Sun Jiao, Pan Zongfu, Song Yu, Zhong Like, Zhang Yiwen, Liu Yujia, Zheng Xiaowei, Huang Ping
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, China.
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, China
Am J Physiol Gastrointest Liver Physiol. 2017 Aug 1;313(2):G150-G156. doi: 10.1152/ajpgi.00426.2016. Epub 2017 May 19.
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 IκB 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 IκB. 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/IκB, 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. 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-IκB axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC.
长链非编码RNA核富集丰富转录本1（NEAT1）在多种癌症的发病机制和发展过程中发挥着重要作用。然而，NEAT1在肝细胞癌（HCC）中的功能机制仍不清楚。通过定量PCR对HCC组织和细胞系中NEAT1和微小RNA（miR）-129-5p的表达进行定量分析。从细胞活力和凋亡方面分析HCC细胞系中NEAT1表达抑制或上调的影响。使用生物软件预测NEAT1与miR-129-5p的结合位点。采用蛋白质免疫印迹法检测miR-129-5p靶分子含缬酪肽蛋白（VCP）和IκB的表达。在移植性肝癌小鼠模型中观察NEAT1对肿瘤生长的影响。在本研究中，得出以下结论：NEAT1在HCC组织和细胞系中的表达显著增加。同时，在HepG2/Huh7细胞系中下调NEAT1表达后，细胞活力显著降低，而相应的凋亡率显著增加。此外，发现NEAT1与miR-129-5p在HCC组织中的表达呈负相关。进一步证明NEAT1与miR-129-5p之间存在一定的负调控机制，这与VCP和IκB的表达有关。小鼠模型实验证实干扰NEAT1表达可抑制肿瘤生长。该研究得出结论，NEAT1的过表达通过调节VCP/IκB抑制miR-129-5p的表达，从而促进HCC细胞的增殖。本研究为HCC的发病机制提供了新的见解，并确定了新的诊断和治疗靶基因。结果提供了有力证据，表明上调的NEAT1促进肝细胞癌（HCC）中癌细胞的增殖，且这种调控机制依赖于微小RNA（miR）-129-5p-含缬酪肽蛋白-IκB轴。该研究还表明NEAT1可能是HCC的潜在治疗靶点。
