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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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4322991 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma.

Zhang Jiwei J Fei Bojian B Wang Qifeng Q Song Mingxu M Yin Yuan Y Zhang Binbin B Ni Shujuan S Guo Weijie W Bian Zehua Z Quan Chao C Liu Zhihui Z Wang Yugang Y Yu Jian J Du Xiang X Hua Dong D Huang Zhaohui Z

Oncotarget 20141201 23

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 progn ...[more]

PMID: 25301729

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Project description:The present study aimed to investigate the expression of miR-200b and protein kinase Cα (PKCα) in pituitary tumors and to determine whether miR-200b may inhibit proliferation and invasion of pituitary tumor cells. The regulation of PKCα expression was targeted in order to find novel targets for the treatment of pituitary tumors. In total, 53 pituitary tumor tissue samples were collected; these included 28 cases of invasive pituitary tumors and 25 cases of non-invasive tumors, in addition to 5 normal pituitaries. The expression level of miR-200b in the pituitary tumor tissue was detected by quantitative polymerase chain reaction (qPCR) and the expression of PKCα protein was detected by immunohistochemistry. A PKCα 3'untranslated region (UTR) luciferase vector was constructed and a dual luciferase reporter gene assay was employed in order to examine the effect of miR-200b on the PKCα 3'UTR luciferase activity. AtT-20 cells were transfected with miR-200b mimics, PKCα siRNA and miR-200b mimics + PKCα, and the changes in cellular proliferation, invasion and apoptosis were observed via MTT, Transwell assay and flow cytometric analysis. Furthermore, PKCα mRNA expression was determined by qPCR, and Western blotting was performed to detect the expression of PKCα protein. miR-200b revealed downregulation in invasive pituitary tumor tissue, and the expression level was significantly down-regulated compared with normal and non-invasive pituitary tumor tissue (P<0.01). In addition, the positive rate of PKCα protein expression in invasive pituitary tumor tissues was significantly higher than in normal and non-invasive tissues (P<0.01). PKCα protein levels are inversely correlated with miR-200b levels in invasive pituitary tumor tissues (r=-0.436, P=0.021). The dual luciferase reporter gene assay revealed that miR-200b could specifically bind to the 3'UTR of PKCα and significantly inhibit the luciferase activity by 39% (P<0.01). Upregulation of miR-200b or downregulation of PKCα could suppress cell proliferation and invasion, and increase apoptosis of AtT-20 cells. It was revealed that PKCα siRNA could suppress both proliferation and invasion of AtT-20 cells and partially simulate the function of miR-200b. Expression of PKCα mRNA and protein decreased significantly in AtT-20 cells overexpressing miR-200b. Additionally, miR-200b was significantly down-regulated in invasive pituitary tumor tissue and inversely correlated with PKCα protein levels. In conclusion, miR-200b inhibited proliferation and invasiveness and promoted the apoptosis of pituitary tumor cells by targeting PKCα. The observations of the present study indicate that miR-200b and PKCα may serve as promising therapeutic targets for invasive pituitary tumors.

Dataset Information

MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma.

Publications

MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma.

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