title: Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer.
abstract: 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/gene-protein/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.
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zou
authors.affiliation: Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Yin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1