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Quantitative Proteomics Reveals the Regulatory Networks of Circular RNA CDR1as in Hepatocellular Carcinoma Cells
Journal of Proteome Research ( IF 4.4 ) Pub Date : 2017-09-20 00:00:00 , DOI: 10.1021/acs.jproteome.7b00519
Xue Yang 1, 2 , Qian Xiong 1 , Ying Wu 1, 2 , Siting Li 1, 2 , Feng Ge 1
Affiliation  

Circular RNAs (circRNAs), a class of widespread endogenous RNAs, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Cerebellar-degeneration-related protein 1 antisense RNA (CDR1as), an oncogenic circRNA, is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying CDR1as functions in HCC remain unclear. Here we explored the functions of CDR1as and searched for CDR1as-regulated proteins in HCC cells. A quantitative proteomics strategy was employed to globally identify CDR1as-regulated proteins in HCC cells. In total, we identified 330 differentially expressed proteins (DEPs) upon enhanced CDR1as expression in HepG2 cells, indicating that they could be proteins regulated by CDR1as. Bioinformatic analysis revealed that many DEPs were involved in cell proliferation and the cell cycle. Further functional studies of epidermal growth factor receptor (EGFR) found that CDR1as exerts its effects on cell proliferation at least in part through the regulation of EGFR expression. We further confirmed that CDR1as could inhibit the expression of microRNA-7 (miR-7). EGFR is a validated target of miR-7; therefore, CDR1as may exert its function by regulating EGFR expression via targeting miR-7 in HCC cells. Taken together, we revealed novel functions and underlying mechanisms of CDR1as in HCC cells. This study serves as the first proteome-wide analysis of a circRNA-regulated protein in cells and provides a reliable and highly efficient method for globally identifying circRNA-regulated proteins.

中文翻译:

定量蛋白质组学揭示了肝癌细胞中环状RNA CDR1as的调控网络。

环状RNA(circRNA)是一类广泛的内源性RNA,在多种生物过程中起着至关重要的作用,并且是多种人类疾病和癌症中的潜在生物标记。小脑变性相关蛋白1反义RNA(CDR1as)是一种致癌性circRNA,与人类肿瘤发生有关,在肝细胞癌(HCC)中表达异常。然而,尚不清楚CDR1as在肝癌中发挥功能的分子机制。在这里,我们探索了CDR1as的功能,并在HCC细胞中寻找CDR1as调控的蛋白。定量蛋白质组学策略用于全局鉴定HCC细胞中CDR1as调控的蛋白。总体而言,我们在HepG2细胞中增强CDR1as表达后鉴定出330种差异表达的蛋白(DEP),表明它们可能是受CDR1as调控的蛋白。生物信息学分析表明,许多DEP参与细胞增殖和细胞周期。对表皮生长因子受体(EGFR)的进一步功能研究发现,CDR1as至少部分通过调节EGFR表达来发挥其对细胞增殖的作用。我们进一步证实,CDR1as可以抑制microRNA-7(miR-7)的表达。EGFR是miR-7的有效靶标;因此,CDR1as可以通过靶向HCC细胞中的miR-7调节EGFR表达来发挥其功能。综上所述,我们揭示了HCC细胞中CDR1as的新功能和潜在机制。这项研究是细胞中circRNA调控蛋白的首次蛋白质组分析,并为全球鉴定circRNA调控蛋白提供了可靠而高效的方法。
更新日期:2017-09-20
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