Lung cancer is one of the most common cancers and its incidence is rising around the world. Various studies suggest that miR-330 acts as a tumor-suppressor microRNA (miRNA) in different types of cancers, but precisely how has remained unclear. In this study, we investigate miR-330 expression in lung cancer patient samples, as well as in vitro, by studying how normalization of miR-330 expression affects lung cancer cellular phenotypes such as viability, apoptosis, proliferation, and migration. We establish that low miR-330 expression predicts poor lung cancer prognosis. Stable restoration of reduced miR-330 expression in lung cancer cells reduces cell viability, increases the fraction of apoptotic cells, causes G2/M cell cycle arrest, and inhibits cell migration. These findings are substantiated by increased mRNA and protein expression of markers for apoptosis via the intrinsic pathway, such as caspase 9, and decreased mRNA and protein expression of markers for cell migration, such as vimentin, C-X-C chemokine receptor type 4, and matrix metalloproteinase 9. We showed that reduced miR-330 expression predicts poor lung cancer survival and that stable restoration of miR-330 expression in lung cancer cells has a broad range of tumor-suppressive effects. This indicates that miR-330 is a promising candidate for miRNA replacement therapy for lung cancer patients.
Purpose: Breast cancer is one of the most commonly diagnosed types of cancer worldwide. This cancer is treated with various methods like mastectomy, chemotherapy, hormone replacement therapy, and radiotherapy. Among them, targeted therapy, which specifically targets cancerous cells by using strategies like microRNA replacement therapy, is considered a new approach in treating breast cancer. Methods: Data analysis from TCGA datasets were used to confirm the decreased expression of miR-146a in breast cancer. MTT assay was used to evaluate the viability of MDA-MB-231 cells after miR-146a restoration. A wound-healing assay was used to observe migration in the MDA-MB-231 cell line and the effect of miR-146a on the migration. Finally, qRT-PCR was used as a method to determine the effect of miR-146a on the expression of CXCR4, β-catenin, MMP2, MMP9, and Vimentin genes are known to be involved in invasion and migration in MDA-MB-231 cell lines in breast cancer. Results: The bioinformatic study showed miR-146a expression decreased in breast tumors compared to adjusted normally. Our results indicated that miR-146a is not involved in apoptosis in the MDA-MB-231 cell line, while it is highly effective in migration inhibition. MMP9, MMP2, CXCR4, and Vimentin expressions were suppressed by miR-146a induction; however, it induced the expression of β-catenin which all result in inhibition of migration. Conclusion: Regulatory molecules, such as miR-146a, are effective in breast cancer targeted therapy. As cancer is a complicated disorder, therefore the combination of therapies, based on these targets might lead to novel therapeutic strategies.
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