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

被引:37
作者
Shirafkan, Naghmeh [1 ,2 ,3 ]
Shomali, Navid [1 ,2 ]
Kazemi, Tohid [2 ]
Shanehbandi, Dariush [1 ]
Ghasabi, Mehri [1 ,2 ]
Baghbani, Elham [1 ]
Ganji, Maziar [4 ]
Khaze, Vahid [1 ]
Mansoori, Behzad [1 ]
Baradaran, Behzad [1 ]
机构
[1] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran
[2] Tabriz Univ Med Sci, Dept Immunol, Fac Med, Tabriz, Iran
[3] Tabriz Univ Med Sci, Student Res Comm, Tabriz, Iran
[4] Shahid Beheshti Univ Med Sci, Dept Med Genet, Fac Med, Tehran, Iran
关键词
colorectal cancer; CXCR4; metastasis; microRNA; miR-193a-5p; vimentin; LYMPH-NODE METASTASIS; COLORECTAL-CANCER; VIMENTIN EXPRESSION; TUMOR-SUPPRESSOR; DOWN-REGULATION; POOR-PROGNOSIS; PROMOTES; MIR-193A-3P; MICRORNAS; CXCR4;
D O I
10.1002/jcb.28164
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:8775 / 8783
页数:9
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