miR-383-5p 通过抑制 PD-L1 抑制乳腺癌细胞增殖、迁移并促进其凋亡。
MicroRNA -383-5p restrains the proliferation and migration of breast cancer cells and promotes apoptosis via inhibition of PD-L1.
机构信息
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Life Sci. 2021 Feb 15;267:118939. doi: 10.1016/j.lfs.2020.118939. Epub 2020 Dec 23.
AIMS
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.
MAIN METHODS
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.
KEY FINDINGS
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.
SIGNIFICANCE
Overall, miR-383-5p can be a promising therapeutic agent for treating breast cancer.
目的
微小 RNA（miRs）在乳腺癌的发展中起着关键作用。miRs 的失调与 PD-L1 介导的免疫抑制有关。本研究旨在探讨转染 miR-383-5p 对乳腺癌细胞和 T 细胞的影响及其与受影响患者临床病理特征的关系。
主要方法
首先，研究了乳腺癌组织中 miR-383-5p 和 PD-L1 的表达水平。然后，用 miR-383-5p 模拟物转染 MDA-MB-231 细胞进行分析。使用 MTT 测定法研究细胞活力，并用 Annexin V/PI 染色法检测细胞凋亡诱导。此外，分别使用划痕愈合试验和流式细胞术分析 miR-383-5p 对细胞迁移和细胞周期进程的影响。使用 qRT-PCR 和 Western blot 研究基因和蛋白质表达。最后，研究了 miR-383-5p 对与癌细胞共培养的 T 细胞的影响。
主要发现
与非恶性组织相比，乳腺癌组织中 PD-L1 上调，miR-383-5p 表达下调。此外，miR-383-5p 通过诱导细胞凋亡和调节凋亡相关基因的表达来降低乳腺癌细胞活力。此外，miR-383-5p 可以通过下调转移相关基因来抑制乳腺癌细胞的迁移。此外，转染的 miR-383-5p 诱导 T 细胞分泌促炎细胞因子。此外，结果表明，miR-383-5p 可能通过抑制 PI3K/AKT/mTOR 通路发挥其肿瘤抑制作用。转染 miR-383-5p 对 PI3K/AKT/mTOR 通路的抑制作用可能是抑制肿瘤 PD-L1 表达的潜在机制。
意义
总体而言，miR-383-5p 可能是治疗乳腺癌的有前途的治疗剂。
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