title: Septin 2 accelerates the progression of biliary tract cancer and is negatively regulated by mir-140-5p.
abstract: Aberrant expression of septin family members (SEPTs) has been noticed in various carcinomas; however, few studies have been conducted to determine their function in biliary tract cancer (BTC). In this study, we identified SEPT2 as a tumor-promoting gene that is regulated by miR-140-5p in BTC. Although miR-140-5p has been reported to be an anti-oncomiR for several types of cancer, this has not previously been shown for BTC. We found that the expression levels of SEPT2 and miR-140-5p were inversely correlated; SEPT2 was aberrantly upregulated in both primary tumor specimens and cell lines whereas miR-140-5p was significantly downregulated. Ectopic expression of miR-140-5p markedly decreased SEPT2 protein concentration in BTC cells and suppressed cell proliferation and colony formation in vitro. Interaction between miR-140-5p and the 3'UTR of SEPT2 was confirmed by luciferase assays and rescue experiments. Furthermore, overexpression of SEPT2 and low expression of miR-140-5p were associated with increased invasion of BTC as indicated by clinical parameters and confirmed by invasion assays in vitro. Xenografts formation assay also showed that SEPT2 overexpression significantly facilitated the growth of tumor in vivo. This finding may provide a novel therapeutic strategy for the treatment of biliary tract cancer.
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Molecular Medicine and Clinical Laboratory, Shaoxing Second Hospital, Shaoxing, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Peitu
authors.initials: P
authors.lastname: Ren
authors.affiliation: Department of Hepatobiliary Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
authors.forename: Baochun
authors.initials: B
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000818:Animals; D001483:Base Sequence; D001661:Biliary Tract Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011485:Protein Binding; D058112:Septins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D008156:Luciferases; C000602252:SEPTIN2 protein, human; D058112:Septins
keywords: Biliary malignancy; Cholangiocarcinoma; Gallbladder cancer; SEPT2; miR-140-5p