Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells
Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells
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宫颈癌细胞中长链非编码 RNA BANCR 调控网络的系统调查
DOI：
10.1021/acs.jproteome.2c00009
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发表时间：
2022
影响因子：
4.4
通讯作者：
Feng Ge
中科院分区：
文献类型：
--
作者：
Bing Wang;Min Wang;Shuzhao Jia;Tao Li;Mingkun Yang;Feng Ge
长非编码RNA(LncRNAs)被认为是人类癌症的功能调节因子。BRAF激活的非编码RNA(BANCR)是一种致癌的非编码RNA，在多种癌症中具有致癌作用。然而，BANCR在宫颈癌中的临床意义和分子机制尚不清楚。在这里，我们通过CRISPR/Cas9编辑建立了BANCR基因敲除细胞系，并揭示了BANCR在HeLa细胞的凋亡、增殖和迁移中发挥作用。采用定量蛋白质组学方法对HeLa细胞中受BANCR调控的蛋白质进行了全局鉴定。总共，我们在HeLa细胞中鉴定了569个BANCR基因敲除后的差异表达蛋白(DEP)。生物信息学分析表明，这些DEPS参与了不同的细胞通路。功能研究表明，BANCR通过调节cAMP反应元件结合蛋白1(CREB1)的表达而影响HeLa细胞的增殖和凋亡。从机制上讲，BANCR可以抑制miR-582-5p的表达，而CREB1是miR-582-5p的直接靶点，因此BANCR可能通过靶向miR-582-5p来调节宫颈癌细胞中CREB1的表达而发挥作用。总之，这项研究建立了一个蛋白质组范围的BANCR调控网络，为宫颈癌的分子发病机制提供了新的见解，并可作为靶向治疗的发展基础。
Long noncoding RNAs (lncRNAs) are increasingly recognized as functional regulators of human cancers. BRAF-activated noncoding RNA (BANCR), an oncogenic lncRNA, has a carcinogenic effect on many types of cancers. However, the clinical significance and molecular mechanisms of BANCR in cervical cancer are still unclear. Here, we generated BANCR knockout cell linesviaCRISPR/Cas9 editing and revealed that BANCR plays roles in the apoptosis, proliferation, and migration of HeLa cells. A quantitative proteomics strategy was employed to globally identify BANCR-regulated proteins in HeLa cells. In total, we identified 569 differentially expressed proteins (DEPs) upon knockout of BANCR in HeLa cells. Bioinformatic analysis revealed that these DEPs were involved in diverse cellular pathways. Functional studies revealed that BANCR exerts its effects on the proliferation and apoptosis of HeLa cells through the regulation of cAMP-responsive element binding protein 1 (CREB1) expression. Mechanistically, BANCR could inhibit the expression of miR-582-5p, and CREB1 is a direct target of miR-582-5p; therefore, BANCR may exert its function by regulating CREB1 expressionviatargeting miR-582-5p in cervical cancer cells. Collectively, this study established a proteome-wide BANCR regulatory network, which provides novel insight into the molecular pathogenesis of cervical cancer and can serve as a basis for the development of targeted therapies.