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假基因 PDIA3P1 通过调节 p53 通路促进肝癌细胞增殖、迁移和侵袭,抑制细胞凋亡。

Pseudogene PDIA3P1 promotes cell proliferation, migration and invasion, and suppresses apoptosis in hepatocellular carcinoma by regulating the p53 pathway.

机构信息

Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

State Key Laboratory & Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Cancer Lett. 2017 Oct 28;407:76-83. doi: 10.1016/j.canlet.2017.07.031. Epub 2017 Aug 18.

Abstract

Pseudogenes are a subclass of long non-coding (lnc) RNAs that arose from protein-coding genes, but have lost the ability to produce proteins. Pseudogenes play an important role in the pathogenesis of various tumors; however, the role of pseudogenes in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated a novel pseudogene, PDIA3P1, which was upregulated in HCC tissues compared with paired normal adjacent tissues. The expression of PDIA3P1 was significantly correlated with tumor size, metastasis, TNM stage, and overall stage. Knockdown of PDIA3P1decreased proliferation, migration, and invasion of HCC cells. PDIA3P1 knockdown also promoted cell apoptosis and inhibited tumor growth in vivo. We performed a GeneChip assay to investigate the underlying mechanism of PDIA3P1 action on biological function, and our results suggested that PDIA3P1 may promote proliferation and inhibit apoptosis of liver cancer cells by inhibiting the p53 pathway. Thus, our data suggest that PDIA3P1 acts as an oncogene in HCC and could be a potential prognostic marker and therapeutic target for HCC.

摘要

假基因是一类长链非编码 (lnc) RNA,它们起源于编码蛋白质的基因,但失去了产生蛋白质的能力。假基因在各种肿瘤的发病机制中发挥着重要作用;然而,假基因在肝细胞癌 (HCC) 中的作用还知之甚少。在这项研究中,我们研究了一种新型假基因 PDIA3P1,它在 HCC 组织中的表达水平高于配对的正常相邻组织。PDIA3P1 的表达与肿瘤大小、转移、TNM 分期和总分期显著相关。PDIA3P1 的敲低降低了 HCC 细胞的增殖、迁移和侵袭。PDIA3P1 的敲低还促进了细胞凋亡并抑制了体内肿瘤的生长。我们进行了 GeneChip 检测,以研究 PDIA3P1 对生物学功能的作用机制,我们的结果表明 PDIA3P1 可能通过抑制 p53 通路促进肝癌细胞的增殖并抑制细胞凋亡。因此,我们的数据表明 PDIA3P1 在 HCC 中发挥癌基因的作用,可能成为 HCC 的潜在预后标志物和治疗靶点。

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