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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Colorectal Cancer | Research

Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK

Authors: Chaofan Peng, Yuqian Tan, Peng Yang, Kangpeng Jin, Chuan Zhang, Wen Peng, Lu Wang, Jiahui Zhou, Ranran Chen, Tuo Wang, Chi Jin, Jiangzhou Ji, Yifei Feng, Junwei Tang, Yueming Sun

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Background

Recent studies have investigated the role of circular RNAs (circRNAs) as significant regulatory factors in multiple cancer progression. Nevertheless, the biological functions of circRNAs and the underlying mechanisms by which they regulate colorectal cancer (CRC) progression remain unclear.

Methods

A novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of circ-GALNT16 in CRC. The FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were performed to investigate the molecular mechanisms of circ-GALNT16 in CRC progression.

Results

Circ-GALNT16 was downregulated in CRC and was negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which promoted the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the formation of the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO-specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex.

Conclusions

Circ-GALNT16 suppressed CRC progression by inhibiting Serpine1 expression through regulating the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might function as a biomarker and therapeutic target for CRC.
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Metadata
Title
Circ-GALNT16 restrains colorectal cancer progression by enhancing the SUMOylation of hnRNPK
Authors
Chaofan Peng
Yuqian Tan
Peng Yang
Kangpeng Jin
Chuan Zhang
Wen Peng
Lu Wang
Jiahui Zhou
Ranran Chen
Tuo Wang
Chi Jin
Jiangzhou Ji
Yifei Feng
Junwei Tang
Yueming Sun
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-021-02074-7

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