MiR-493 by regulating of c-Jun targets Wnt5a/PD-L1-inducing esophageal cancer cell development.

Wei Bian,Hao Zhang,Yishuai Li,Shujun Li,Chuan Wang,Ren Niu,Shaolin Gao,Haiyong Zhu,Xuebo Qin

doi:10.1111/1759-7714.13950

Abstract

BackgroundEsophageal cancer is one of the most common cancers across the globe; the 5‐year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development.MethodsThrough experiments in vivo and in vitro, we explored potential signaling pathways, miR‐493/Wnt5A/c‐JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens.ResultsOverexpression of miR‐493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR‐493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR‐493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR‐493 inhibits the activity of c‐JUN and p‐PI3K/p‐AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c‐JUN binds the promoter region of miR‐493 and suppressed the expression of miR‐493, forming a negative feedback loop.ConclusionsThe miR‐493/Wnt5A/c‐JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.

Highlights

MiRNA dysregulation has been implicated in cancer development.Methods In the present study, we use cell culture and transfection, the tissue specimens, RNA isolation and Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and so on to explore the role of miR-493 in esophageal cancer.Results Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro
More than five-fold increase in miR493 expression was observed in EC9706 and TE13 cells treated with miR-493 mimics compared with the negative control (NC) group by quantitative real time polymerase chain reaction (qRT-PCR) (Supplementary Figure. 1A)
Results showed that miR-493 overexpression significantly reduced the ability of esophageal cancer (EC) cell migration and invasion (Figure. 1D, E and F)

Summary

Introduction

MiRNA dysregulation has been implicated in cancer development.Methods In the present study, we use cell culture and transfection, the tissue specimens, RNA isolation and RT-PCR, Western blot and so on to explore the role of miR-493 in esophageal cancer.Results Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. MiR-493 regulates the expression of PD-L1 by c-JUN and the sensitivity of EC cells to DDP.Conclusions the results elucidate a molecular feedback loop that involves miR-493, Wnt5A, c-JUN and PD-L1 in EC. In future, these mechanistic findings provide a useful therapeutic option for the treatment of EC. MiR-493 suppresses tumor growth, invasion and metastasis of lung cancer, and enforced expression of miR-493 in lung cancer cells promotes chemotherapy sensitivity to cisplatin [13,14,15]. We studied the role of miR-493 and its underlying regulatory mechanisms in EC

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Discussion

Conclusion