Abstract
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 of miR-196b-5p in NSCLC progression and metastasis still remains unclear. We found that miR-196b-5p promotes 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 the miR-196b-5p expression. 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 that miR-196b-5p might exhibit novel oncogenic function by FAS-mediated STAT3 activation in NSCLC, and suggested that targeting the miR-196b-5p/FAS/NFkB/IL6/STAT3 pathway might be a promising therapeutic strategy in treating NSCLC.
Highlights
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, with ~2.1 million new lung cancer cases and 1.8 million deaths were reported in 20181
Upregulated miR-196b-5p inhibits FAS expression in non-small cell lung cancer (NSCLC) Recently, we found that miR-196b-5p functions as an oncomiRNA in NSCLC by directly targeting GATA6 and TSPAN1219
We found that higher miR-196b-5p expression in NSCLC tissues than those in normal adjacent tissues (NATs) (Fig. 1a)
Summary
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide, with ~2.1 million new lung cancer cases and 1.8 million deaths were reported in 20181. Non-small cell lung cancer (NSCLC) accounts for ~80–85% of all lung cancer cases. Several targeted therapies were available for patients with NSCLC; most of them are only effective in treating cancer patients with certain genetic backgrounds. MicroRNAs (miRNAs), a class of small noncoding. RNAs, play a key role in cancer pathogenesis by targeting specific mRNAs4,5. Most of miRNAs function as a tumor suppressor or oncogene in a tissue-specific manner[5]. Accumulating evidence indicated that the dysregulation of miRNAs was closely associated with NSCLC progression and metastasis[7]. MiR-34 inhibits tumor immune evasion to suppress NSCLC progression by targeting PD-L18. MiR-548a-3p has been reported to regulate the Warburg effect and NSCLC growth by inhibiting transcription factor SIX19. MiR-34 inhibits tumor immune evasion to suppress NSCLC progression by targeting PD-L18. miR-548a-3p has been reported to regulate the Warburg effect and NSCLC growth by inhibiting transcription factor SIX19. let-7, a tumor suppressor in breast cancer, reduces breast tumor-initiating
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