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Anticancer Res. 2017 Aug;37(8):4345-4352.

miR-141 Inhibits Proliferation and Migration of Colorectal Cancer SW480 Cells.

Author information

1
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Xi-Cheng District, Beijing, P.R. China.
2
School of Rehabilitation, Capital Medical University, Department of General Surgery, Beijing Bo'ai Hospital, China Rehabilitation Research Center, Beijing, P.R. China.
3
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Xi-Cheng District, Beijing, P.R. China zhangzht@medmail.com.cn yj232325@sina.com.

Abstract

BACKGROUND:

This study was designed to determine the molecular function of miR-141 and the underlying mechanisms in colorectal cancer (CRC).

MATERIALS AND METHODS:

SW480 cells in which miR-141 was up- or down-regulated were established. Reverse transcription, quantitative polymerase chain reaction and Western blotting were used to examine the microRNA and protein expression. Cell-cycle progression was analyzed by flow cytometry. Proliferation marker Ki-67 was evaluated by immunofluorescence. Transwell assay was conducted to determine the migration rates of cells. Subcutaneous xenograft models were used to examine the effect of miR-141 on tumorigenicity. Human mitogen-activated protein kinase (MAPK) and receptor tyrosine kinase (RTK) pathway phosphorylation array assays were used to interrogate MAPK and RTK pathway activation.

RESULTS:

miR-141 directly targeted zinc finger E-box-binding homeobox 1/2 (ZEB1/2). We first determined the expression levels of ZEB1 and ZEB2 in miR-141-expressing cells and miR-141-knockdown cells and found that inhibition of miR-141 significantly increased the expression of ZEB2. In vitro study revealed that miR-141 overexpression inhibited the expression of Ki-67. Furthermore, overexpression of miR-141 led to a significant reduction in the proliferation of SW480 cells via induction of cell-cycle arrest at the G1 stage. In contrast, inhibition of miR-141 markedly promoted the proliferation of SW480 cells by promoting cell-cycle progression. Moreover, overexpression of miR-141 significantly inhibited SW480 cell migration in vitro. In addition, overexpression of miR-141 significantly reduced tumor size and weight, and inhibited the growth of SW480 cell-derived tumor in nude mice. Notably, overexpression of miR-141 also suppressed the liver metastasis of SW480 cells in nude mice. Using RTK and MAPK arrays, we found increased phosphorylation of hepatocyte growth factor receptor (HGFR/c-MET) following inhibition of miR-141, but phosphorylation of P53, AKT, ERK1/2, P38 and mTOR, etc., in SW480 cells was not affected by miR-141.

CONCLUSION:

Our results suggest that miR-141 functions as a tumor suppressor through ZEB2 and HGFR in CRC cells.

KEYWORDS:

colorectal cancer (CRC); metastasis; miR-141; microRNA

PMID:
28739727
DOI:
10.21873/anticanres.11828
[Indexed for MEDLINE]

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