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)
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)
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蛋白质组学和转录组学综合分析揭示长非编码 RNA HOX 转录反义基因间 RNA (HOTAIR) 通过调节阿片类生长因子受体 (OGFr) 促进肝细胞癌细胞增殖
DOI：
10.1074/mcp.ra117.000277
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发表时间：
2018-01-01
影响因子：
7
通讯作者：
Ge, Feng
中科院分区：
文献类型：
--
作者：
Wu, Ying;Xiong, Qian;Ge, Feng
长链非编码RNA HOX转录反义RNA（HOTAIR）参与人类肿瘤发生，并在肝细胞癌（HCC）中失调。然而，HOTAIR在肝癌中发挥作用的分子机制在很大程度上尚不清楚。在这里，我们采用了整合的转录组学和定量蛋白质组学分析，系统地探讨HOTAIR在肝癌中的调节作用。HOTAIR抑制后，共发现673个转录本和293个蛋白质表达异常。生物信息学研究表明，差异表达基因（DEG）和差异表达蛋白（DEPs）参与了许多生物学过程，尤其是与肿瘤相关的信号通路。一组DEG和DEP分别通过定量RT-PCR、Western blot和平行反应监测（PRM）分析进行验证。阿片样生长因子受体（OGFr）是HCC中细胞增殖的负生物调节因子，对OGFr的进一步功能研究表明，HOTAIR至少部分通过调节OGFr表达对细胞增殖发挥作用。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。
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.