title: MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma.
abstract: The expression of miR-638 was found downregulated in colorectal carcinoma (CRC) in our previous study. However, the role of miR-638 in CRC remains unknown. The aim of this study was to determine the function and mechanism of miR-638 in CRC. Here, we verified that miR-638 was frequently downregulated in CRC tissues compared with corresponding noncancerous tissues (NCTs) in an expanded CRC cohort, and survival analysis showed that the downregulation of miR-638 in CRC was associated with poor prognoses. The ectopic expression of miR-638 inhibited CRC cell proliferation, invasion and arrest the cell cycle in G1 phase, whereas the repression of miR-638 significantly promoted CRC cell growth, invasion and cell cycle G1/S transition. Subsequent mechanism analyses revealed that miR-638 inhibited CRC cell growth, invasion and cell cycle progression by targeting TSPAN1. TSPAN1 protein levels were upregulated in CRC samples and were inversely correlated with miR-638 levels. More importantly, high TSPAN1 expression levels in CRC tissues predicted poor overall survival, and appears to be an independent prognostic factor for CRC survival. Furthermore, CpG island methylation analyses revealed that the miR-638 promoter was hypermethylated in CRC and that attenuating promoter methylation was sufficient to restore miR-638 expression in CRC cells. Taken together, our current data demonstrate that miR-638 functions as a tumor suppressor in human CRC by inhibiting TSPAN1, and that TSPAN1 is a potential prognostic factor for CRC.
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Bojian
authors.initials: B
authors.lastname: Fei
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Mingxu
authors.initials: M
authors.lastname: Song
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Ni
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Guo
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Quan
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-5942, USA.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D059470:Tetraspanins / Q000096:biosynthesis*; D059467:Transcriptome
chemical_list: C572154:MIRN638 microRNA, human; D035683:MicroRNAs; C508125:TSPAN1 protein, human; D059470:Tetraspanins