title: Overexpression of TRPV3 Correlates with Tumor Progression in Non-Small Cell Lung Cancer.
abstract: (1) BACKGROUND: Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP channels family of Ca(2+)-permeant channels. The proteins of some TRP channels are highly expressed in cancer cells. This study aimed to assess the clinical significance and biological functions of TRPV3 in non-small cell lung cancer (NSCLC); (2) METHODS: Immunohistochemistry was used to detect the expression of TRPV3 in NSCLC tissues and adjacent noncancerous lung tissues. Western blot was used to detect the protein expressions of TRPV3, CaMKII, p-CaMKII, CyclinA, CyclinD, CyclinE1, CDK2, CDK4, and P27. Small interfering RNA was used to deplete TRPV3 expression. A laser scanning confocal microscope was used to measure intracellular calcium concentration ([Ca(2+)]i). Flow cytometry was used to analyze cell cycle; (3) RESULTS: TRPV3 was overexpressed in 65 of 96 (67.7%) human lung cancer cases and correlated with differentiation (p = 0.001) and TNM stage (p = 0.004). Importantly, TRPV3 expression was associated with short overall survival. In addition, blocking or knockdown of TRPV3 could inhibit lung cancer cell proliferation. Moreover, TRPV3 inhibition could decrease [Ca(2+)]i of lung cancer cells and arrest cell cycle at the G1/S boundary. Further results revealed that TRPV3 inhibition decreased expressions of p-CaMKII, CyclinA, CyclinD1, CyclinE, and increased P27 level; (4) CONCLUSIONS: Our findings demonstrate that TRPV3 was overexpressed in NSCLC and correlated with lung cancer progression. TRPV3 activation could promote proliferation of lung cancer cells. TRPV3 might serve as a potential companion drug target in NSCLC.
authors.affiliation: Department of Pathology, Harbin Medical University-Daqing, Daqing 163319, China. xiaoleili2004@163.com.|Department of Scientific Research, Third Affiliated Hospital of Guizhou Medical University, Duyun 558000, China. xiaoleili2004@163.com.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. maomaozqh@sina.com.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Harbin Medical University-Daqing, Daqing 163319, China. katie8213@sina.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Harbin Medical University, Harbin 150081, China. liyingxu2004@126.com.
authors.forename: Baiyan
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pathology, Daqing General Hospital Group Oilfield General Hospital, Daqing 163319, China. car_fast_2003@163.com.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. 18385653360@163.com.
authors.forename: Hanping
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. songbaili@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. caoyonggang417@aliyun.com.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Daqing 163319, China. hlsun2002@163.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
mesh_terms: D000072283:A549 Cells; D000368:Aged; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; D002118:Calcium
keywords: TRPV3; [Ca2+]i; cell cycle; non-small cell lung cancer; proliferation