MicroRNA-199a-5p suppresses cell proliferation, migration and invasion by targeting ITGA3 in colorectal cancer

As a member of the integrin family, integrin alpha 3 beta 1 (ITGA3) has been linked to intercellular communication and serves an important role in the signaling among cells and the extracellular matrix. MicroRNA (miR)-199a-5p has been demonstrated to be related to the pathogenesis and progression of multiple malignant diseases. However, the biological functions of miR-199a-5p and ITGA3 in colorectal cancer (CRC) have rarely been reported. The aim of the present study was to explore the roles of miR-199a-5p and ITGA3 in CRC. Immunohistochemistry staining and western blotting were applied to detect the protein expression of ITGA3 in CRC tissues and cells. Reverse transcription-quantitative PCR was performed to investigate the expression of miR-199a-5p and ITGA3 mRNA. HCT-116 cells were transfected with miR-199a-5p mimics, mimics control, short hairpin RNA targeting ITGA3, or pcDNA-ITGA3 for the functional experiments. Dual luciferase reporter assay was applied to confirm whether miR-199a-5p targeted the 3 ' untranslated region (3 ' UTR) of ITGA3. The MTT, Transwell and wound healing assays were used to evaluate the proliferation, invasion and migration of CRC cells. Immunofluorescence assay was used to monitor the epithelial-mesenchymal transition (EMT) biomarker expression. The results demonstrated downregulation of miR-199a-5p and upregulation of ITGA3 in CRC tissues and cell lines. miR-199a-5p mimics and knockdown of ITGA3 suppressed the proliferation, invasion and migration of CRC cells. Bioinformatics analysis and luciferase reporter assay indicated that miR-199a-5p targeted the 3 ' UTR of the ITGA3 transcript, and overexpression of ITGA3 reversed the tumor-suppressive effects of miR-199a-5p elevation. In addition, the immunofluorescence assay suggested that miR-199a-5p mimics suppressed the EMT of CRC cells, whereas the overexpression of ITGA3 restored this effect. In conclusion, miR-199a-5p may act as a tumor suppressor by targeting and negatively regulating ITGA3 in CRC.