title: Lentivirus-mediated shRNA interference of ghrelin receptor blocks proliferation in the colorectal cancer cells.
abstract: Ghrelin, an orexigenic peptide, acts via the growth hormone secretagogue receptor (GHSR) to stimulate the release of growth hormone. Moreover, it has a range of biological actions, including the stimulation of food intake, modulation of insulin signaling and cardiovascular effects. Recently, it has been demonstrated that ghrelin has a proliferative and antiapoptotic effects in cancers, suggesting a potential role in promoting tumor growth. However, it remains unknown whether GHSR contributes to colorectal cancer proliferation. In this study, the therapeutic effect of lentivirus-mediated short hairpin RNA (shRNA) targeting ghrelin receptor 1a (GHSR1a) was analyzed in colorectal cancer cell line SW480 both in vitro and in vivo. Our study demonstrated that ghrelin and GHSR1a are significantly upregulated in cancerous colorectal tissue samples and cell lines. In vitro, human colorectal cancer cell line SW480 with downregulation of GHSR1a by shRNA showed significant inhibition of cell viability compared with blank control (BC) or scrambled control (SC) regardless of the application of exogenous ghrelin. Furthermore, GHSR1a silencing by target specific shRNA was shown capable of increasing PTEN, inhibiting AKT phosphorylation and promoting the release of p53 in SW480 cells. In addition, the effects of GHSR1a knockdown were further explored in vivo using colorectal tumor xenograft mouse model. The tumor weights were decreased markedly in GHSR1α knockdown SW480 mouse xenograft tumors compared with blank control or negative control tumors. Our results suggested that the expression of GHSR1a is significantly correlated with the growth of colorectal cancer cells, and the GHSR1a knockdown approach may be a potential therapy for the treatment of colorectal cancer.
authors.affiliation: Department of General Surgery, The First People Hospital of Yueyang, 39 Dong mao ling Road, Yueyang, Hunan, 325000, China. hosrml@qq.com.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The First People Hospital of Yueyang, 39 Dong mao ling Road, Yueyang, Hunan, 325000, China.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The First People Hospital of Yueyang, 39 Dong mao ling Road, Yueyang, Hunan, 325000, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The First People Hospital of Yueyang, 39 Dong mao ling Road, Yueyang, Hunan, 325000, China.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014161:Transduction, Genetic
chemical_list: D034741:RNA, Small Interfering; D054440:Receptors, Ghrelin; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase
keywords: Colorectal cancer; PTEN; ghrelin; growth hormone secretagogue receptor; proliferation