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长链非编码 RNA PCAT6 预测肝癌预后不良,并通过调节细胞周期停滞和凋亡促进增殖。

LncRNA PCAT6 predicts poor prognosis in hepatocellular carcinoma and promotes proliferation through the regulation of cell cycle arrest and apoptosis.

机构信息

Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.

Cancer Center, Southern Medical University, Guangzhou, China.

出版信息

Cell Biochem Funct. 2020 Oct;38(7):895-904. doi: 10.1002/cbf.3510. Epub 2020 Feb 16.

Abstract

Long noncoding RNAs have been proved in regulating tumourigenesis, including hepatocellular carcinoma (HCC). However, up to date, the role of PCAT6 in HCC is rare to be reported. In current study, bioinformatics analysis and quantitative real-time PCR were applied to examine the expression of PCAT6 in HCC. The role of PCAT6 in cell proliferation, cell cycle arrest, apoptosis, and metastasis were detected in both gain- and loss-of-function studies by cell biological assays. Bioinformatics analysis was employed to investigate the PCAT6-related genes and pathways in HCC. And we found that PCAT6 was significantly upregulated in HCC tissues and correlated with poor overall survival and disease-free survival in HCC patients. Furthermore, elevated PCAT6 promoted cell proliferation, inhibited cell cycle arrest and cell apoptosis while deficiency of PCAT6 impaired cell proliferation, caused cell cycle arrest and induced cell apoptosis of HCC. Moreover, as for bioinformatics analysis, a total of 389 PCAT6-related genes were found in both HCC tissue and cell lines, and these promising target genes were highly enriched in various key pathways, such as Wnt, HIF-1 signalling pathway, and metabolic pathways. Additionally, among these genes, DCAF13, SNRPB2, RPS8, and FKBP1A were revealed to be overexpressed in HCC and predicted poor prognosis. Taken together, our findings illustrate that PCAT6 contributes to HCC progression and might be a potential target for HCC therapy. Bioinformatics analysis may present a new way for assessing the underlying mechanism of PCAT6 in HCC. SIGNIFICANCE OF THE STUDY: Hepatocellular carcinoma (HCC) is one of the most common and malignant tumours all over the world. In this study, we observed that PCAT6 was upregulated in HCC and correlated with poor prognosis of HCC patients. PCAT6 could promote cell proliferation, inhibit cell cycle arrest and cell apoptosis of HCC, suggesting PCAT6 exerts tumorigenic role in HCC. Moreover, bioinformatics analysis revealed a total of 389 PCAT6-related genes in both HCC tissue and cell lines, and these promising target genes were highly enriched in various key pathways, such as Wnt, HIF-1 signalling pathway, and metabolic pathways. These finding provided evidence that PACT6 may be identified as a strategy to treat HCC in the future.

摘要

长链非编码 RNA 已被证明在调节肿瘤发生中起作用,包括肝细胞癌 (HCC)。然而,迄今为止,PCAT6 在 HCC 中的作用很少有报道。在本研究中,应用生物信息学分析和实时定量 PCR 检测 HCC 中 PCAT6 的表达。通过细胞生物学检测,在功能获得和功能丧失研究中检测 PCAT6 在细胞增殖、细胞周期阻滞、细胞凋亡和转移中的作用。应用生物信息学分析研究 HCC 中 PCAT6 相关基因和通路。我们发现 PCAT6 在 HCC 组织中显著上调,并与 HCC 患者的总生存率和无病生存率差相关。此外,升高的 PCAT6 促进细胞增殖,抑制细胞周期阻滞和细胞凋亡,而 PCAT6 的缺乏则损害细胞增殖,导致 HCC 细胞周期阻滞和诱导细胞凋亡。此外,对于生物信息学分析,在 HCC 组织和细胞系中总共发现了 389 个与 PCAT6 相关的基因,这些有前途的靶基因高度富集在各种关键通路中,如 Wnt、HIF-1 信号通路和代谢通路。此外,在这些基因中,DCAF13、SNRPB2、RPS8 和 FKBP1A 在 HCC 中过度表达,并预测预后不良。总之,我们的研究结果表明,PCAT6 促进 HCC 进展,可能成为 HCC 治疗的潜在靶点。生物信息学分析可能为评估 PCAT6 在 HCC 中的潜在机制提供了一种新方法。

研究的意义

肝细胞癌 (HCC) 是全球最常见和最恶性的肿瘤之一。在本研究中,我们观察到 PCAT6 在 HCC 中上调,并与 HCC 患者的预后不良相关。PCAT6 可促进 HCC 细胞的增殖,抑制细胞周期阻滞和细胞凋亡,提示 PCAT6 在 HCC 中发挥致癌作用。此外,生物信息学分析显示,在 HCC 组织和细胞系中共有 389 个与 PCAT6 相关的基因,这些有前途的靶基因高度富集在各种关键通路中,如 Wnt、HIF-1 信号通路和代谢通路。这些发现为 PACT6 可能被确定为未来治疗 HCC 的策略提供了证据。

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