miRNA‐143 replacement therapy harnesses the proliferation and migration of colorectal cancer cells in vitro

Abstract

miR-143 is a tumor suppressor miRNA which its downregulation is frequently reported in colorectal cancer (CRC). This miRNA is a negative regulator of K-RAS, c-MYC, BCL-2, and MMP-9 genes which are engaged in tumor growth and metastasis.In the present study, miR-143 restoration was performed by transfection of the pCMV-miR-143 vector into the SW-480 CRC cells. Subsequently, alterations in proliferative and migratory potential of the cells were investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and wound-healing assays, respectively. Moreover, to detect apoptosis incidence in the transfected cells, 4',6-diamidino-2-phenylindole (DAPI) staining was used. Furthermore, mRNA levels of c-MYC, K-RAS, MMP-9, and BCL-2, as potential targets of miR-143, were assessed by quantitative Real-Time PCR (qRT-PCR). Also the expression levels of c-MYC, K-RAS, and MMP-9 proteins were investigated by the western blot analysis. Finally, the ratio of BAX to BCL-2 expression, as a potential marker of the response to apoptosis stimuli, was compared between the control and test groups. Furthermore, the trypan blue test was performed to determine the cell viability in cell suspension. According to the results, a decreased viability and migratory potential was observed for the miR-143 receiving cells.The DAPI staining also confirmed the occurrence of apoptosis. Moreover, BCL-2, K-RAS, MMP-9, and c-MYC mRNAs were significantly downregulated in the miR-143 grafted cells.The BAX/BCL-2 ratio also indicated a notable increase in the cells with miR-143 overexpression. In brief, miR-143 replacement could be considered as an effective strategy for the management of CRC and attenuating its invasive features.

The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells

“…The migration capacity was calculated by evaluating the distance between the wound edges through Image J software. A wound-healing assay was performed in triplicate [32,33].…”

MiR-130a-3p suppresses colorectal cancer growth by targeting Wnt Family Member 1 (WNT1)

“…MiRNAs are multifunctional regulators of tumorigenesis and cancer progression, and miRNAs with tumor suppressor activities have been proposed as adjuvant therapies. These miRNAs, such as miRNA-506-3p, miRNA-143, miRNA-330, miR-141-3p, and miRNA-877 [19][20][21][22][23], inhibit tumorigenesis or progression by targeting oncogenic genes or signaling pathways. Both in vitro and in vivo experiments by Tian et al reported the inhibition of migration and invasion by miR-130a-3p in esophageal squamous cell carcinoma cell line EC-1 [24].…”

Prospects for Manipulation of Mesenchymal Stem Cells in Tumor Therapy: Anti-Angiogenesis Property on the Spotlight

“…Furthermore, MSC-derived EVs containing miRNAs targeting VEGF were observed to suppress angiogenesis in human nasopharyngeal carcinoma cells ( 100 ). miR-143, which has been investigated in several malignancies ( 101 ), was indicated to be harbored by MSC-derived EVs an reduced the migration of osteosarcoma cells ( 102 ). As a consequence, MSC-derived EVs are able to repress the tumor cell proliferation and angiogenesis.…”