Dataset Information

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.

ABSTRACT:

Background

MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated.

Methods

In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice.

Results

MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial-mesenchymal transition (EMT)-associated proteins. TGF-?1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-?1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1.

Conclusions

miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.

SUBMITTER: Zhang P

PROVIDER: S-EPMC5558677 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.

Zhang P P Tang W M WM Zhang H H Li Y Q YQ Peng Y Y Wang J J Liu G N GN Huang X T XT Zhao J J JJ Li G G Li A M AM Bai Y Y Chen Y Y Ren Y X YX Li G X GX Wang Y D YD Liu S D SD Wang J D JD

British journal of cancer 20170620 4

<h4>Background</h4>MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated.<h4>Methods</h4>In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude ...[more]

PMID: 28632723

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Project description:BackgroundWe previously reported an inverse relationship between B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP), which is associated with the prognosis of gastric cancer (GC). In this study, we further explored the microRNA (miRNA) regulatory mechanism between Bmi-1 and RKIP.MethodsMicroarray analysis was first carried out to identify miRNA profiles that were differentially expressed in cells overexpressing Bmi-1. Then, miRNAs that could regulate RKIP were identified. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of Bmi-1, miR-155, miR-27a and RKIP. RKIP was confirmed as a target of miR-27a and miR-155 through luciferase reporter assays, qRT-PCR and Western blotting. The effects of the Bmi-1/miR-27a/RKIP and Bmi-1/miR-155/RKIP axes on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.ResultsThe downregulation of RKIP by Bmi-1 occurred at the protein but not mRNA level. This indicates probable posttranscriptional regulation. miRNA expression profiles of cells with ectopic expression of Bmi-1 were analyzed and compared to those of control cells by microarray analysis. A total of 51 upregulated and 72 downregulated miRNAs were identified. Based on publicly available algorithms, miR-27a and miR-155 were predicted, selected and demonstrated to target RKIP. Bmi-1, miR-27a and miR-155 are elevated in human GC and associated with poor prognosis of GC, while RKIP is expressed at lower levels in GC and correlated with good prognosis. Then, in vitro tests shown that in addition to regulating RKIP expression via miR-27a and miR-155, Bmi-1 was also able to regulate the migration, invasion, proliferation, colony-formation ability and chemosensitivity of GC cells through the same pathway. Finally, the in vivo test showed similar results, whereby the knockdown of the Bmi-1 gene led to the inhibition of tumor growth, metastasis and chemoresistance through miR-27a and miR-155.ConclusionsBmi-1 was proven to induce the expression of miR-27a and miR-155 and thus promote tumor metastasis and chemoresistance by targeting RKIP in GC. Overall, miR-27a and miR-155 might be promising targets for the screening, diagnosis, prognosis, treatment and disease monitoring of GC.

Dataset Information

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.

Background

Methods

Results

Conclusions

Publications

MiR-646 inhibited cell proliferation and EMT-induced metastasis by targeting FOXK1 in gastric cancer.

Similar Datasets

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