MiR-150 promotes cellular metastasis in non-small cell lung cancer by targeting FOXO4

Abstract

Previous studies have shown that dysregulation of microRNA-150 (miR-150) is associated with aberrant proliferation of human non-small cell lung cancer (NSCLC) cells. However, whether miR-150 has a critical role in NSCLC cell metastasis is unknown. Here, we reveal that the critical pro-metastatic role of miR-150 in the regulation of epithelial-mesenchymal-transition (EMT) through down-regulation of FOXO4 in NSCLC. In vitro, miR-150 targets 3′UTR region of FOXO4 mRNA, thereby negatively regulating its expression. Clinically, the expression of miR-150 was frequently up-regulated in metastatic NSCLC cell lines and clinical specimens. Contrarily, FOXO4 was frequently down-regulated in NSCLC cell lines and clinical specimens. Functional studies show that ectopic expression of miR-150 enhanced tumor cell metastasis in vitro and in a mouse xenograft model, and triggered EMT-like changes in NSCLC cells (including E-cadherin repression, N-cadherin and Vimentin induction, and mesenchymal morphology). Correspondingly, FOXO4 knockdown exhibited pro-metastatic and molecular effects resembling the effect of miR-150 over-expression. Moreover, NF-κB/snail/YY1/RKIP circuitry regulated by FOXO4 were likely involved in miR-150-induced EMT event. Simultaneous knockdown of miR-150 and FOXO4 abolished the phenotypic and molecular effects caused by individual knockdown of miR-150. Therefore, our study provides previously unidentified pro-metastatic roles and mechanisms of miR-150 in NSCLC.

Downregulated microRNA‐150 upregulates IRX1 to depress proliferation, migration, and invasion, but boost apoptosis of gastric cancer cells

“…In line with our results, a study by Wu Q et al has proffered that in gastric cancer, overexpressed miR‐150 is capable of boosting cancer cell proliferation and growth partially by modulating EGR2 . Prior research has indicated that elevation of miR‐150 in nonsmall cell lung cancer advances tumor cell metastasis in vitro and in xenograft models of nude mice, and causes epithelial‐mesenchymal transition‐like changes . There has also been report revealing that elevated miR‐150 expression may catalyze prostate cancer stem cell development through restriction of p27 .…”

“…7 Prior research has indicated that elevation of miR-150 in nonsmall cell lung cancer advances tumor cell metastasis in vitro and in xenograft models of nude mice, and causes epithelial-mesenchymal transition-like changes. 24 There has also been report revealing that elevated miR-150 expression may catalyze prostate cancer stem cell development through restriction of p27. 19 A similar report by Zhao Y et al has also proposed the stimulative impacts of miR-150 on prostate cancer.…”

MiR‐150 alleviates neuropathic pain via inhibiting toll‐like receptor 5

“…41 By regulating suppressor of cytokine signaling 3, Downregulation of microRNA-218 can relieve neuropathic pain. 32 These studies have indicated that targeting specific miRNAs can reduce neuropathic pain development. In our current study, we suggested that miR-150 was a novel miRNA which regulated neuropathic pain development.…”

Network Pharmacology Approach Reveals the Potential Immune Function Activation and Tumor Cell Apoptosis Promotion of Xia Qi Decoction in Lung Cancer

“…We analyzed the data and relevant biological processes for LC, choosing top ten remarkable significant pathways ( Figure 5) according to the p value for further study. The first four pathways with the largest number of gene enrichment were cell senescence [50,51], FoxO signaling pathway [52,53], HIF-1 (hypoxia inducible factor) signaling pathway [54], and estrogen signaling pathway [55,56]. Thus pro-senescence therapies may represent a new treatment for lung cancer [57].…”