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. 2019 May;120(5):8775-8783.
doi: 10.1002/jcb.28164. Epub 2018 Dec 2.

microRNA-193a-5p inhibits migration of human HT-29 colon cancer cells via suppression of metastasis pathway

Naghmeh Shirafkan  1   2   3 , Navid Shomali  1   2 , Tohid Kazemi  2 , Dariush Shanehbandi  1 , Mehri Ghasabi  1   2 , Elham Baghbani  1 , Maziar Ganji  4 , Vahid Khaze  1 , Behzad Mansoori  1 , Behzad Baradaran  1
Affiliations

microRNA-193a-5p inhibits migration of human HT-29 colon cancer cells via suppression of metastasis pathway

Naghmeh Shirafkan et al. J Cell Biochem. 2019 May.

Abstract

Purpose: Altered expression of microRNAs (miRNAs) is indicated strongly in colorectal cancer (CRC). This study aims to evaluate the inhibitory role of miR-193a-5p on epithelial-mesenchymal transition markers in CRC lines. The cellular effects and potential mechanisms of miR-193a-5p were also examined.

Methods: Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to determine the expression of miR-193a-5p in three CRC cell lines (HCT-116, SW-480, and HT-29) and its impact on metastasis-related genes ( vimentin and CXCR4) before and after mimic transfection. Of those, the cell line with the highest changes was selected for the next upcoming experiments such as wound-healing assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and annexin-V staining tests.

Results: Our results revealed that miR-193a-5p was significantly downregulated in three CRC cell lines and that HT-29 displayed the most decrease ( P < 0.0001). The restoration of miR-193a-5p in human HT-29 cell line inhibited cell migration. But, miR-193a-5p transfection did not affect cell viability and had no significant effect on apoptosis induction. Also, the quantitative RT-PCR analysis of miR-193a-5p mimic transfected cells revealed a significant increase in miR-193a-5p messenger RNA (mRNA) expression level ( P < 0.0001) with reduction of vimentin and CXCR4 mRNA expression levels in HT-29 cell line ( P < 0.01 and < 0.05, respectively).

Conclusion: Our results indicated that miR-193a-5p acts as a tumor suppressor miRNA and its downregulation plays an important role in metastasis via upregulation of metastasis-related genes in CRC. Therefore, it can be considered as a potential therapeutic target for applying in CRC management in the future.

Keywords: CXCR4; colorectal cancer; metastasis; miR-193a-5p; microRNA; vimentin.

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References

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