title: RNAi targeting of CCR2 gene expression induces apoptosis and inhibits the proliferation, migration, and invasion of PC-3M cells.
abstract: Prostate cancer (PCa) is the second most lethal malignancy in men. It has been reported that chemokines, produced by cancer cells, have linked with tumor progression and metastatic spread. We have proven that chemokine (C-C) motif ligand 2 (CCL2) is involved in the growth and invasion of PCa. In this study, we studied whether CC chemokine receptor 2 (CCR2), the receptor of CCL2, also contributes to PCa progression. We constructed the recombinant plasmid pGCsi-CCR2 and investigated the effects of pGCsi-CCR2 on proliferation, apoptosis, migration, and invasion of PC-3M cells. RT-PCR and Western blot assay showed that transfection with the plasmid pGCsi-CCR2 successfully inhibited the CCR2 expression. The cell proliferation rate was significantly slow, and the apoptotic rate was increased in PC-3M cells treated with CCR2-siRNA, indicated by MTT cell viability and TUNEL assay, respectively. As expected, CCR2 knockdown also reduced the migration and invasion of PC-3M cells, as illustrated through wound-healing assay and Transwell assay. The possible molecular mechanism was the regulation of several signal pathways involved in survival, apoptosis, migration, and metastasis. Altogether, the present finding suggests that CCR2 expression is crucial for CCL2-induced proliferation and invasion of PC-3M cells, and CCR2 could also be a promising molecular target for prevention of PCa growth and metastasis.
authors.affiliation: Department of Urology, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Gao
authors.forename: Anna
authors.initials: A
authors.lastname: Wang
authors.forename: Muchun
authors.initials: M
authors.lastname: Zhang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Kaichen
authors.initials: K
authors.lastname: Wang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Han
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Wang
authors.forename: Chaoling
authors.initials: C
authors.lastname: Shi
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
mesh_terms: D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D054390:Receptors, CCR2 / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection
chemical_list: C515334:CCR2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D054390:Receptors, CCR2