Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer
Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer
复制标题
瞬时受体电位阳离子通道、C 亚族、成员 1 的下调有助于卵巢癌的耐药性和高组织学分级。
DOI：
10.3892/ijo.2015.3254
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发表时间：
2016-01-01
影响因子：
5.2
通讯作者：
Yin, Fuqiang
中科院分区：
文献类型：
--
作者：
Liu, Xia;Zou, Jing;Yin, Fuqiang
瞬时受体电位阳离子通道，亚家族C，成员1（TRPC 1）参与许多生理功能，但也涉及癌症的发展。然而，TRPC 1在卵巢癌（OC）中的作用知之甚少，包括这些肿瘤的耐药性。在本研究中，一个显着的和一致的下调TRPC 1在耐药OC组织/细胞，使用实时定量聚合酶链反应测定和微阵列沉积在Oncomine和基因表达综合（GEO）配置文件。蛋白质/基因蛋白质/基因和蛋白质-化学物质相互作用表明，TRPC 1与14种蛋白质/基因和6种化学物质相互作用，所有这些都参与了OC耐药性的调节。TRPC 1、OC和耐药性的生物学过程注释表明，TRPC 1在OC中的耐药性相关功能中发挥作用，主要通过细胞周期、基因表达和细胞生长与细胞死亡。mRNA-microRNA相互作用分析显示，在11条主要途径中，有8条参与了卵巢癌耐药的调控，其中前10位的microRNA中有8条与卵巢癌和其他癌症的耐药有关。在使用从癌症基因组图谱项目（TCGA）队列中获得的341名OC患者的数据进行的临床分析中，发现TRPC 1表达在2级和3级肿瘤之间存在显著差异，低水平表达与较高的肿瘤分级相关。这是第一份报告显示TRPC 1的下调与OC的耐药性和高组织学肿瘤分级之间的潜在关联。我们的研究结果为进一步研究TRPC 1在OC和其他形式的癌症中的耐药相关功能提供了基础。
Transient receptor potential cation channel, subfamily C, member 1 (TRPC1) participates in many physiological functions but has also been implicated in cancer development. However, little is known about the role of TRPC1 in ovarian cancer (OC), including the drug resistance of these tumors. In the present study, a significant and consistent downregulation of TRPC1 in drug-resistant OC tissues/cells was determined using real-time quantitative polymerase chain reaction assays and the microarrays deposited in Oncomine and Gene Expression Omnibus (GEO) profiles. Protein/geneprotein/gene and protein-chemical interactions indicated that TRPC1 interacts with 14 proteins/genes and 6 chemicals, all of which are involved in the regulation of drug resistance in OC. Biological process annotation of TRPC1, OC, and drug resistance indicated a role for TRPC1 in drug-resistance-related functions in OC, mainly via the cell cycle, gene expression and cell growth and cell death. Analysis of mRNA-microRNA interactions showed that 8 out of 11 major pathways enriched from 38 predominant microRNAs targeting TRPC1 were involved in the regulation of drug resistance in OC, and 8 out of these top 10 microRNAs were implicated in the drug resistance in ovarian and other cancers. In a clinical analysis using data obtained from The Cancer Genome Atlas project (TCGA) cohort on 341 OC patients, TRPC1 expression was found to differ significantly between grade 2 and grade 3 tumors, with low-level expression correlating with higher tumor grade. This is the first report to show a potential association between the downregulation of TRPC1 and both drug resistance and high histological tumor grade in OC. Our results provide the basis for further investigations of the drug-resistance-related functions of TRPC1 in OC and other forms of cancer.