ALKBH5-mediated M6A Modification of CircCCDC134 Facilitates Cervical Cancer Metastasis by Enhancing HIF1A Transcription

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2022 Aug 26

PMID 36028854

Authors

Leilei Liang

Yunshu Zhu

Jian Li

Jia Zeng

Lingying Wu

Affiliations

Soon will be listed here.

Abstract

Background: Metastasis is the main cause of mortality in cervical cancer (CC). Circular RNAs (circRNAs) have been demonstrated to play a crucial role in carcinoma biology. However, the expression and function of circRNAs in cervical cancer metastasis are still unclear.

Methods: In the present study, we identified a circRNA with an N6-methyladenosine (m6A) modification, circCCDC134, whose expression was increased in CC tissues by circRNA-Seq and qPCR. CircCCDC134 upregulation in CC was fine-tuned by ALKBH5-mediated m6A modification, which enhanced its stability in a YTHDF2-dependent manner. The functional experiments illustrated that circCCDC134 enhanced tumour proliferation and metastasis in vitro and in vivo. For the comprehensive identification of RNA-binding proteins, circRNA pull-down and mass spectrometry (ChIRP-MS), chromatin immunoprecipitation-seq (Chip-seq), RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays were used to perform mechanistic investigations.

Results: The results revealed that circCCDC134 recruited p65 in the nucleus and acted as a miR-503-5p sponge to regulate the expression of MYB in the cytoplasm, ultimately stimulating HIF1A transcription and facilitating CC growth and metastasis.

Conclusion: These findings indicate that circCCDC134 is an important therapeutic target and provide new regulatory model insights for exploring the carcinogenic mechanism of circCCDC134 in CC.

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