Microrna 130b Suppresses Migration and Invasion of Colorectal Cancer Cells through Downregulation of Integrin β1

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.

MiR-30a-5p Suppresses Tumor Metastasis of Human Colorectal Cancer by Targeting ITGB3

“…In another study, reactive oxygen species were shown to markedly upregulate the expression of ITGB3, promoting a more aggressive phenotype in a colorectal cancer cell line with increased migratory and invasive capacities [47]. MiRNAs have been linked with the dysregulation of integrin signaling in a number of studies, correlating miRNA-regulated integrin signaling with tumor metastasis and apoptosis in CRC [28], as well as breast, hepatocellular and salivary adenoid cystic carcinoma [7,48,49]. Our findings provide further evidence of the targeting of integrins by miRNAs.…”

“…Studies have shown that miRNA-30a can act as a tumor suppressor, inducing growth inhibition and suppression of cell migration and invasion in CRC, by targeting denticleless protein homolog, PIK3CD and insulin receptor substrate 2 [25][26][27]. miRNAs have also been reported to modulate the expression of integrins, transmembrane receptors involved in signal transduction, and dysfunction in miRNA-regulated integrin signaling has been linked to tumor metastasis and apoptosis in a number of cancers including CRC [28].…”

Detection of Circulating miRNA Levels in Schizophrenia

“…Functional studies of these miRNAs would be helpful for a better understanding of their contribution to the pathophysiology of schizophrenia. The validated downstream target genes for miR-130b include PDGFRA, RUNX3, ITGB1, PPARG, FMR1, and STAT3, and for miR-193a-3p they include ErbB4, S6K2, and MCL1 (33)(34)(35)(36)(37)(38)(39). These genes can be classified into three groups: schizophrenia susceptibility genes (PDGFRA, PPARG, ErbB4), neurodevelopment-related genes (RUNX3, ITGB1, FMR1, STAT3), and neuroprotective genes (S6K2 and MCL1).…”

Repression of microRNA-130b by thyroid hormone enhances cell motility

“…A recent study by Zhao et al [25] demonstrated that ectopic expression of miR-130b suppresses cell proliferation and invasion through inhibition of STAT3 in pancreatic cancer. Another group [26] reported that miR-130b reduces cell migration and invasion through inhibition of integrin β1 in colorectal cancer. The collective evidence implies a tumor suppressor role of miR-130 in metastasis.…”