miR-409 Inhibits Human Non-Small-Cell Lung Cancer Progression by Directly Targeting SPIN1.
miR-409 Inhibits Human Non-Small-Cell Lung Cancer Progression by Directly Targeting SPIN1.
复制标题
miR-409 通过直接靶向 SPIN1 抑制人类非小细胞肺癌进展
DOI：
10.1016/j.omtn.2018.08.020
复制
发表时间：
2018-12-07
期刊：
影响因子：
--
通讯作者：
Jiao S
中科院分区：
文献类型：
--
作者：
Song Q;Ji Q;Xiao J;Li F;Wang L;Chen Y;Xu Y;Jiao S
肺癌是世界范围内癌症死亡的主要原因，具有高转移潜力的特点。越来越多的证据表明Spindlin 1(Spindlin 1，SPIN1)参与了肿瘤的发展和癌变。然而，SPIN1在非小细胞肺癌(NSCLC)中的作用以及SPIN1在人类NSCLC中的分子机制尚不清楚。我们检测了SPIN1在人NSCLC中的功能，发现SPIN1的表达与NSCLC患者的总体生存和不良预后密切相关。MicroRNAs的异常调控(MiRNAs)在肿瘤进展中起着重要作用。我们发现miR-409通过直接与SPIN1的3‘非编码区结合来抑制SPIN1的表达。在体外和体内，miR-409的过表达通过抑制SPIN1显著抑制细胞的迁移、生长和增殖。在miR-409转基因的NSCLC细胞中过表达SPIN1有效地挽救了miR-409调控的细胞迁移、生长和增殖的抑制。MIR-409在非小细胞肺癌中调节PI3K/AKT(蛋白激酶B)通路。此外，临床数据显示，miR-409水平高的非小细胞肺癌患者的存活率显著提高。MIR-409表达与SPIN1表达呈负相关。综上所述，这些发现表明miR-409/SPIN1轴是一个有用的多向调节网络，可以早期预测NSCLC患者的转移潜能，提示miR-409和SPIN1可能是治疗NSCLC患者有吸引力的预后标志物。
Lung cancers, the leading cause of cancer mortality worldwide, are characterized by a high metastatic potential. Growing evidence reveals that Spindlin 1 (SPIN1) is involved in tumor progression and carcinogenesis. However, the role of SPIN1 in non-small-cell lung cancer (NSCLC) and the molecular mechanisms underlying SPIN1 in human NSCLC remain undetermined. Here we examined the function of SPIN1 in human NSCLC and found that the expression of SPIN1 was closely correlated with the overall survival and poor prognosis of NSCLC patients. Aberrant regulation of microRNAs (miRNAs) has an important role in cancer progression. We revealed that miR-409 inhibits the expression of SPIN1 by binding directly to the 3′ UTR of SPIN1 using dual-luciferase reporter assays. Overexpression of miR-409 significantly suppressed cell migration, growth, and proliferation by inhibiting SPIN1 in vitro and in vivo. SPIN1 overexpression in miR-409-transfected NSCLC cells effectively rescued the suppression of cell migration, growth, and proliferation regulated by miR-409. miR-409 regulates the PI3K/AKT (protein kinase B) pathway in NSCLC. Moreover, clinical data showed that NSCLC patients with high levels of miR-409 experienced significantly better survival. miR-409 expression was also negatively associated with SPIN1 expression. Taken together, these findings highlight that the miR-409/SPIN1 axis is a useful pleiotropic regulatory network and could predict the metastatic potential in NSCLC patients early, indicating the possibility that miR-409 and SPIN1 might be attractive prognostic markers for treating NSCLC patients.
登录
查看更多内容
影响因子：
1.6
作者：
Jiang, FG;Zhao, QA;Rao, ZH
通讯作者：
Rao, ZH
影响因子：
5.3
作者：
Brute, Stephanie Y.;Al-Baimani, Khalid;Wheatley-Price, Paul
通讯作者：
Wheatley-Price, Paul
影响因子：
4
作者：
Choi, Jeong-Woo;Zhao, Ming-Hui;Cui, Xiang-Shun
通讯作者：
Cui, Xiang-Shun
组蛋白代码读取器SPIN1控制骨骼肌的发育。
影响因子：
9
作者：
Greschik H;Duteil D;Messaddeq N;Willmann D;Arrigoni L;Sum M;Jung M;Metzger D;Manke T;Günther T;Schüle R
通讯作者：
Schüle R
影响因子：
5.6
作者：
Li L;Zhu T;Gao YF;Zheng W;Wang CJ;Xiao L;Huang MS;Yin JY;Zhou HH;Liu ZQ
通讯作者：
Liu ZQ