miR-410 通过调控 SOCS3/JAK-STAT 信号通路影响肺癌 A549 细胞的增殖和凋亡。
MiR-410 affects the proliferation and apoptosis of lung cancer A549 cells through regulation of SOCS3/JAK-STAT signaling pathway.
机构信息
Department of Respiration, Yantai Yeda Hospital, Yantai, Shandong, China.
出版信息
Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):5987-5993. doi: 10.26355/eurrev_201809_15933.
OBJECTIVE
Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signal pathway participates in regulating cell proliferation, differentiation, and apoptosis, and is correlated with non-small cell lung cancer (NSCLC) onset. Suppressors of cytokine signaling 3 (SOCS3) negatively regulates JAK-STAT pathway. SOCS3 is down-regulated in NSCLC tissues, with an elevation of miR-410 expression. This study thus intends to investigate if miR-410 plays a role in mediating NSCLC onset and underlying mechanism in this regulatory process.
PATIENTS AND METHODS
NSCLC patients were collected for tumor and adjacent tissues, among which, miR-410 and SOCS3 expression were measured. Dual luciferase reporter gene assay was employed to confirm the targeting relationship between miR-410 and SOCS3. Their expression levels were compared between A549 and BEAS-2B cells. Cultured A549 cells were treated with anti-miR-410 and/or SOCS3. Expression levels of SOCS3, p-JAK1/2, p-STAT3, and Bcl-2 were compared along with the apoptotic rate of cells.
RESULTS
Bioinformatics analysis revealed targeted binding site between miR-410 and 3'-UTR of SOCS3 mRNA. Compared to those in tumor tissues, a significant increase of miR-410 and reduction of SOCS3 were found in NSCLC tissue (p < 0.05). Dual luciferase reporter gene assay indicated that SOCS3 was targeted regulated by miR-410. Significantly higher miR-410 and lower SOCS3 levels were shown in A549 cells, compared to those in BEAS-2B cells. Transfection of anti-miR-410 and/or SOCS3 in A549 cells, SOCS3 expression and apoptosis were significantly induced, while JAK1, JAK2, and STAT3 phosphorylation were statistically decreased with the reduction of the Bcl-2 level (p < 0.05).
CONCLUSIONS
miR-410 level was increased while SOCS3 expression was declined in NSCLS tissues. MiR-410 induces the apoptosis of A549 cells through downregulating JAK/STAT3/SOCS3 signaling pathway, which provides new insights for the therapy of pulmonary carcinoma in clinic.
目的
Janus 激酶（JAK）-信号转导子和转录激活子（STAT）信号通路参与调节细胞增殖、分化和凋亡，与非小细胞肺癌（NSCLC）的发生有关。细胞因子信号转导抑制因子 3（SOCS3）负调控 JAK-STAT 通路。SOCS3 在 NSCLC 组织中下调，miR-410 表达升高。本研究旨在探讨 miR-410 是否在介导 NSCLC 发生及其在该调控过程中的潜在机制中发挥作用。
患者和方法
收集 NSCLC 患者的肿瘤和相邻组织，测量 miR-410 和 SOCS3 的表达。采用双荧光素酶报告基因检测证实 miR-410 与 SOCS3 之间的靶向关系。比较 A549 和 BEAS-2B 细胞中两者的表达水平。用抗 miR-410 和/或 SOCS3 处理培养的 A549 细胞。比较 SOCS3、p-JAK1/2、p-STAT3 和 Bcl-2 的表达水平以及细胞的凋亡率。
结果
生物信息学分析显示 miR-410 与 SOCS3 mRNA 3'-UTR 之间存在靶向结合位点。与肿瘤组织相比，NSCLC 组织中 miR-410 显著增加，SOCS3 减少（p < 0.05）。双荧光素酶报告基因检测表明 SOCS3 受 miR-410 靶向调控。与 BEAS-2B 细胞相比，A549 细胞中 miR-410 水平显著升高，SOCS3 水平显著降低。在 A549 细胞中转染抗 miR-410 和/或 SOCS3，SOCS3 表达和细胞凋亡明显增加，而 JAK1、JAK2 和 STAT3 磷酸化明显降低，Bcl-2 水平降低（p < 0.05）。
结论
NSCLS 组织中 miR-410 水平升高，SOCS3 表达下调。miR-410 通过下调 JAK/STAT3/SOCS3 信号通路诱导 A549 细胞凋亡，为临床治疗肺癌提供了新的思路。
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