MicroRNA-146a induces immune suppression and drug-resistant colorectal cancer cells

• Published in: Tumor biology Vol. 39; no. 5; p. 1010428317698365
• Main Authors: Khorrami, Samaneh, Zavaran Hosseini, Ahmad, Mowla, Seyed Javad, Soleimani, Masoud, Rakhshani, Naser, Malekzadeh, Reza
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-05-2017; Sage Publications Ltd; IOS Press
• Subjects: 5-Fluorouracil; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Authorship; Breast cancer; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Cancer therapies; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Cycle Checkpoints - immunology; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Cytokines; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug Resistance, Neoplasm - immunology; Fluorouracil - administration & dosage; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - immunology; HEK293 Cells; HT29 Cells; Humans; Immunoregulation; Inflammation; Interleukin 10; Irinotecan; Lentivirus - genetics; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocytes; Lymphocytes T; MicroRNAs - biosynthesis; MicroRNAs - genetics; MicroRNAs - immunology; miRNA; Ovarian cancer; Peripheral blood mononuclear cells; Polyethylene glycol; Stem cells; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Transfection; Transforming growth factor; Transforming growth factor-b; Viruses; Iran; United States > US; miR-146a; drug resistance; immune regulation; Colorectal cancer
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1177/1010428317698365

Recent studies underline the involvement of microRNAs in cancer development through induction of immune suppression milieu and evolution of drug resistance. The goal of this study was to evaluate the effects of miR-146a on regulatory T cells’ frequencies, T-lymphocyte proliferation, and cytokine expression as well as drug resistance in cancer cells. We found that miR-146a was overexpressed in colon cancer HT-29 cells. Peripheral blood mononuclear cells were obtained from healthy donors and were co-cultured with transfected HT-29 cells. Afterward, peripheral blood mononuclear cell proliferation, expression of anti-inflammatory cytokines, and regulatory T cells’ frequencies were assayed. Also, drug resistance in transfected HT-29 cells was analyzed following treatment with 5-fluorouracil and irinotecan. Overexpression of miR-146a increased transforming growth factor-β and interleukin-10 expressions and enhanced regulatory T cells’ frequencies in peripheral blood mononuclear cells. Also, the number of cells undergoing cell cycle arrest and apoptosis significantly decreased in transfected HT-29 cancer cells. In conclusion, upregulation of miR-146a plays an important role in enhancing immune suppression through increasing the regulatory T cells’ population. Also, our data indicated that colon cancer drug resistance is possibly associated with miR-146a overexpression.