Abstract

MicroRNA 130b (miR-130b) is significantly dysregulated in various human tumor types. In this study, using a microarray assay, we characterized the upregulation of miR-130b expression in colorectal cancer (CRC) specimens. However, there is limited knowledge about the roles of aberrant miR-130b expression in CRC. Our studies in CRC cells demonstrated that miR-130b significantly decreases cell migration and invasion, but it has no evidently effects on cell proliferation and apoptosis. In the overexpression miR-130b CRC cells and the CRC specimens, we observed a decreased level of integrin β1 protein, which is considered as a key molecule involved in cell motility. The targeting of the 3′-UTR region of integrin β1 gene by miR-130b was revealed using a luciferase reporter assay. The regulation of integrin β1 by miR-130b was further shown using the miR-130b mimics and the inhibitor of miR-130b. The impaired motility of the miR-130b overexpression cells is recovered partly by the expression of integrin β1 lacking the 3′-UTR. Additionally, the knockdown of integrin β1 also gives rise to a decrease in cell migration and invasion, which is similar to the impeded motility due to overexpression of miR-130b in CRC cells. Furthermore, the inverse expressions of miR-130b and integrin β1 were observed in CRC specimens. In summary, these data demonstrate that miR-130b downregulates its target-integrin β1, leading to the impaired migration and invasion of CRC cells.

Highlights

  • MicroRNAs are short non-coding RNAs of 24 to 25 nucleotides that mediate gene silencing through imperfect hybridization to 39 untranslated region (39-UTR) in target mRNAs [1]

  • MiR-130b decreases migration and invasion of CRC cells We examined how miR-130b might function inside colorectal cancer cells

  • The decrease of cell motility is achieved through the suppression of integrin b1 expression. These findings demonstrated that miR-130b suppresses cell migration and invasion, at least in part, through downregulation of integrin b1 in CRC cells

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Summary

Introduction

MicroRNAs (miRNA) are short non-coding RNAs of 24 to 25 nucleotides that mediate gene silencing through imperfect hybridization to 39 untranslated region (39-UTR) in target mRNAs [1]. The metastatic process follows of a series of steps: first, cancer cells within the primary tumor break away from neighboring cells and invade the basement membrane. This local invasion may frequently be triggered by contextual signals that causing cancer cells to undergo an epithelialmesenchymal transition (EMT) [11]. We compared miRNA expression in specimens from CRC patients using a microRNA microarray and observed the significant upregulation of miR-130b expressed in the CRC specimens. MiR-130b and the downregulation of integrin b1 by miR-130b leads to the impaired migration and invasion of CRC cells

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