MicroRNA -383-5p restrains the proliferation and migration of breast cancer cells and promotes apoptosis via inhibition of PD-L1

• Published in: Life sciences (1973) 2021-02, Vol.267, p.118939-118939, Article 118939
• Main Authors: Azarbarzin, Shirin, Hosseinpour-Feizi, Mohammad Ali, Banan Khojasteh, Seyed Mahdi, Baradaran, Behzad, Safaralizadeh, Reza
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Annexin V; Apoptosis; Apoptosis - physiology; Assaying; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; carcinogenesis; Cell cycle; Cell Line, Tumor; Cell migration; cell movement; Cell Movement - physiology; Cell proliferation; Cell Proliferation - physiology; Cell Survival - physiology; Cell viability; Chemical compounds; Chromosome 5; coculture; Cytokines; Female; Flow cytometry; Gene expression; Gene flow; Genes; Humans; Inflammation; Lymphocytes T; MDA-MB-231; Metastases; microRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miR-383-5P; miRNA; neoplasm cells; PD-L1; PD-L1 protein; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT/mTOR; Proto-Oncogene Proteins c-akt - metabolism; secretion; Signal Transduction - genetics; T-cell; T-lymphocytes; therapeutics; Tissues; TOR protein; TOR Serine-Threonine Kinases - metabolism; toxicity testing; Western blotting; Wound healing
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118939

MicroRNAs (miRs) play pivotal roles in breast cancer development. The dysregulation of miRs has been associated with PD-L1-mediated immune suppression. This study aimed to examine the effect of transfected miR-383-5p on breast cancer cells and T-cells and its association with clinicopathological features in affected patients. Initially, miR-383-5p and PD-L1 expression levels were investigated in breast cancer tissues. Then, MDA-MB-231 cells were transfected with miR-383-5p mimics to perform analyses. Cell viability was investigated using the MTT assay, and the annexin V/PI staining assay was performed to examine apoptosis induction. Furthermore, the effect of miR-383-5p on cell migration and cell cycle progression was analyzed using the wound-healing assay and flow cytometry, respectively. Gene and protein expressions were studied using qRT-PCR and western blotting. Finally, the effect of miR-383-5p on T-cells, which were co-cultured with cancer cells, was investigated. Compared to non-malignant tissues, PD-L1 was up-regulated, and miR-383-5p expression was downregulated in breast cancer tissues. Moreover, miR-383-5p reduced breast cancer cell viability via inducing apoptosis and modulating the expression of apoptosis-related genes. Besides, miR-383-5p could inhibit the migration of breast cancer cells via down-regulating metastasis-related genes. Besides, transfected miR-383-5p induced the secretion of pro-inflammatory cytokines from T-cells. Furthermore, the results showed that miR-383-5p might exert its tumor-suppressive effect via inhibiting the PI3K/AKT/mTOR pathway. The inhibitory effect of transfected miR-383-5p on the PI3K/AKT/mTOR pathway might be the underlying mechanism for inhibiting tumoral PD-L1 expression. Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer. •MiR-383-5P is downregulated in breast cancer and functions as a tumor suppressor.•MiR-383-5p replacement inhibited cell migration and proliferation, and promoted apoptosis via targeting PD-L1.•MiR-383-5P modulated the activity of PI3K/AKT/mTOR pathway.•MiR-383-5p induced the secretion of pro-inflammatory cytokines from T-cells.