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整合蛋白质组学和转录组学分析揭示长非编码 RNA HOX 转录反义基因间 RNA(HOTAIR)通过调节阿片样生长因子受体(OGFr)促进肝癌细胞增殖。

Integrated Proteomic and Transcriptomic Analysis Reveals Long Noncoding RNA HOX Transcript Antisense Intergenic RNA (HOTAIR) Promotes Hepatocellular Carcinoma Cell Proliferation by Regulating Opioid Growth Factor Receptor (OGFr).

机构信息

From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

§University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Mol Cell Proteomics. 2018 Jan;17(1):146-159. doi: 10.1074/mcp.RA117.000277. Epub 2017 Oct 27.

Abstract

Long noncoding RNA HOX transcript antisense RNA (HOTAIR) is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HOTAIR functions in HCC are largely unknown. Here, we employed an integrated transcriptomic and quantitative proteomic analysis to systematically explore the regulatory role of HOTAIR in HCC. A total of 673 transcripts and 293 proteins were found to be dysregulated after HOTAIR inhibition. Bioinformatics studies indicated that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) are involved in many biological processes, especially cancer-related signaling pathways. A set of DEGs and DEPs were validated by quantitative RT-PCR, Western blot and parallel reaction monitoring (PRM) analysis, respectively. Further functional studies of the opioid growth factor receptor (OGFr), a negative biological regulator of cell proliferation in HCC, revealed that HOTAIR exerts its effects on cell proliferation, at least in part, through the regulation of OGFr expression. By correlating the omics data with functional studies, the current results provide novel insights into the functional mechanisms of HOTAIR in HCC cells.

摘要

长链非编码 RNA HOX 转录反义 RNA(HOTAIR)参与人类肿瘤发生,在肝细胞癌(HCC)中失调。然而,HOTAIR 在 HCC 中的功能的分子机制在很大程度上是未知的。在这里,我们采用了综合转录组学和定量蛋白质组学分析来系统地研究 HOTAIR 在 HCC 中的调节作用。在抑制 HOTAIR 后,共发现 673 个转录物和 293 个蛋白质失调。生物信息学研究表明,差异表达基因(DEGs)和差异表达蛋白(DEPs)参与许多生物学过程,特别是与癌症相关的信号通路。通过定量 RT-PCR、Western blot 和平行反应监测(PRM)分析分别验证了一组 DEGs 和 DEPs。进一步研究阿片生长因子受体(OGFr)的功能,OGFr 是 HCC 中细胞增殖的负性生物学调节剂,表明 HOTAIR 通过调节 OGFr 的表达对细胞增殖产生影响。通过将组学数据与功能研究相关联,目前的结果为 HOTAIR 在 HCC 细胞中的功能机制提供了新的见解。

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