Inhibition of miR‑483‑5p improves the proliferation, invasion and inflammatory response of triple‑negative breast cancer cells by targeting SOCS3

• Published in: Experimental and therapeutic medicine 2021-10, Vol.22 (4), Article 1047
• Main Authors: Ren, Jianbo, Xu, Gang, Sun, Hongyan, Lin, Ting, Xu, Sanhui, Zhao, Yating
• Format: Article
• Language: English
• Subjects: Apoptosis; Biotechnology; Breast cancer; Cancer; Care and treatment; Cell proliferation; Cellular signal transduction; Colorectal cancer; Development and progression; Genetic aspects; Health aspects; Inflammation; Medical prognosis; Metastasis; MicroRNA; MicroRNAs; Oncology, Experimental; Proteins
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2021.10480

microRNAs (miRs) have been indicated to serve oncogenic or tumor suppressor roles. However, the role of miR-483-5p in breast cancer and its associated molecular mechanisms remain unclear. In the present study, compared with adjacent normal tissues and MCF-10a cells, the expression level of miR-483-5p was upregulated in triple-negative breast cancer (TNBC) tissues and TNBC cell lines. Bioinformatic analysis and luciferase reporter assay confirmed the presence of miR-483-5p binding sites in the 3'-untranslated region of suppressor of cytokine signaling 3 (SOCS3). In addition, the expression level of SOCS3 protein in TNBC tissues was markedly lower compared with in adjacent tissues, and miR-483-5p expression was negatively correlated with SOCS3 expression in TNBC tissues. Cell proliferation and flow cytometry assays indicated that knockdown of miR-483-5p inhibited the proliferation and promoted apoptosis in the TNBC cell line BT-549. This effect was markedly attenuated by SOCS3 small interfering (si)RNA transfection. Additionally, wound healing and Transwell assays demonstrated that SOCS3 siRNA reversed the inhibitory effects of miR-483-5p inhibitor on the migration and invasion of BT-549 cells. Moreover, the decrease in miR-483-5p expression significantly reduced the secretion of TNF-[alpha], IL-6, IL-1[beta] and monocyte chemoattractant protein-1 in BT-549 cells, while SOCS3 siRNA could partially reverse this effect. Additionally, SOCS3 overexpression reversed the effects of miR-483-5p mimic on the proliferation, migration, invasion and inflammation of BT-549 cells. Taken together, these data demonstrated that the inhibition of miR-483-5p could inhibit the proliferation, migration, invasion and inflammatory response, while promoting the apoptosis of TNBC cells by negatively regulating SOCS3. miR-483-5p may be a potential target for TNBC therapy. Key words: triple negative breast cancer, microRNA-483-5p, inflammatory response, suppressor of cytokine signaling 3