CTCF-silenced miR-137 contributes to EMT and radioresistance in esophageal squamous cell carcinoma

Shuwen Xu,Aonan Du,Zhiwei Lu,Hua Hui,Yufeng Wang,Chong Geng,Xiaofeng Li,Qiang Wang,Tao Zhang,Longfei Li,Feng Guo

doi:10.1186/s12935-020-01740-8

Shuwen Xu, Aonan Du + Show 9 more

Open Access

https://doi.org/10.1186/s12935-020-01740-8

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Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. However, the role of miR-137 has not been fully revealed in ESCC.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were separately used to examine RNA level and protein level. 5-ethynyl-2′-deoxyuridine (EdU) assay, transwell assays and flow cytometry analyses were conducted to assess biological behaviors of ESCC cells. Additionally, the interaction between genes were analyzed via Chromatin Immunoprecipitation (ChIP) assay, RNA Binding Protein Immunoprecipitation (RIP) assay, RNA pull down assay and luciferase reporter assay.ResultsMiR-137 was down-regulated in ESCC cells. Upregulation of miR-137 hindered ESCC cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT). Besides, miR-137 enhanced the sensitivity of ESCC cells to irradiation. Moreover, CCCTC-binding factor (CTCF) inactivated miR-137 transcription in ESCC cells. Furthermore, we revealed enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and paxillin (PXN) as the downstream targets of miR-137. In turn, EZH2 was recruited by CTCF and induced methylation in miR-137 promoter.ConclusionCTCF/Suz12/EZH2 complex-silenced miR-137 facilitates ESCC progression and radioresistance by targeting EZH2 and PXN.

Highlights

Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system
MiR‐137 is expressed at a low level in ESCC cells and suppresses cell proliferation, migration and radioresistance Firstly, we utilized Quantitative real-time polymerase chain reaction (qRT-PCR) to explore miR-137 expression in ESCC cells
CCCTC-binding factor (CTCF) induces DNA methylation of miR‐137 via recruiting polycomb repressive complex 2 (PRC2) complex Using UCSC, we focused on three potential transcription factors of miR-137, namely, suppressor of zeste 12 homologue (Suz12), Enhancer of zeste homolog 2 (EZH2) and CTCF (Fig. 4a)

Summary

Introduction

Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. Esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) are two Alteration of RNA expression is closely correlated with the progression of human diseases [6, 7]. Non coding RNAs (ncRNAs) have been reported in recent years due to their crucial role in human cancers [8]. Numerous miRNAs have been reported to be dysregulated and is associated with the development of various cancers [13,14,15,16,17,18,19,20,21,22], including EC [23]. The role miR-137 in ESCC progression has never been investigated

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