miR-196b-5p-mediated downregulation of FAS promotes NSCLC progression by activating IL6-STAT3 signaling

被引：41

作者：

Huang, Xiangjie ^{[1
]}

Xiao, Sisi ^{[1
,2
]}

Zhu, Xinping ^{[1
]}

Yu, Yun ^{[1
]}

Cao, Meng ^{[1
]}

Zhang, Xiaodong ^{[2
]}

Li, Shaotang ^{[2
]}

Zhu, Wangyu ^{[3
]}

Wu, Fengjiao ^{[1
]}

Zheng, Xiaohui ^{[1
]}

Jin, Libo ^{[4
,5
]}

Xie, Congying ^{[2
]}

Huang, Xiaoying ^{[2
]}

Zou, Peng ^{[1
,4
,5
]}

Li, Xiaokun ^{[1
,4
,5
]}

Cui, Ri ^{[1
,4
,5
]}

机构：

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Canc & Anticanc Drug Res Ctr, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Sch Pharmaceut Sci, Affiliated Zhoushan Hosp, Wenzhou 325035, Zhejiang, Peoples R China

[4] Wenzhou Univ, Inst Life Sci, Wenzhou 325035, Zhejiang, Peoples R China

[5] Wenzhou Univ, Wenzhou Med Univ, Collaborat Innovat Ctr Biomed, Wenzhou 325035, Zhejiang, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 09期

基金：

中国国家自然科学基金;

关键词：

TUMOR PROGRESSION; LUNG-CANCER; EXPRESSION; CD95; CHEMOKINES; MICRORNAS; APOPTOSIS; PATHWAY; CELLS;

D O I：

10.1038/s41419-020-02997-7

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Our recent study demonstrated that the QKI-5 regulated miRNA,miR-196b-5p, and it functions as an onco-microRNA in non-small cell lung cancer (NSCLC) by directly targeting GATA6 and TSPAN12. However, the role ofmiR-196b-5pin NSCLC progression and metastasis still remains unclear. We found thatmiR-196b-5ppromotes lung cancer cell proliferation and colony formation by directly targeting tumor suppressor, FAS. The expression of FAS was significantly downregulated in NSCLC tissue samples and was negatively correlated with themiR-196b-5pexpression. Knocking down FAS activates NFkB signaling and subsequent IL6 secretion, resulting in phosphorylation of signal transducer and activator of transcription 3 (STAT3) to promote lung cancer cell growth. Our findings indicated thatmiR-196b-5pmight exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting themiR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.

引用

页数：13

共 44 条

[1]

Fas(CD95) induces macrophage proinflammatory chemokine production via a MyD88-dependent, caspase-independent pathway [J].