Cancer Cell International | |
Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression | |
Yin-Yuan Mo1  Wan-Xin Peng1  Jing Jiang2  Ming Lei3  Xinglin Hu4  Di-Xian Luo5  Jia Li6  Zheng Hu6  Weihao Luo6  Rong-Zhang He6  Lili Duan6  | |
[1] Cancer Institute, University of Mississippi Medical Center;Center of Medical Laboratory, The First People’s Hospital of Chenzhou, University of South China;Department of Clinical Laboratory, The First People’s Hospital of Changde City;Department of Dermatology, Affiliated the First People’s Hospital of Chenzhou of University of South China;Department of Laboratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital);Translational Medicine Institute, National and Local Joint Engineering Laboratory for High-Through Molecular Diagnosis Technology, The First People’s Hospital of Chenzhou, The First Affiliated Hospital of Xiangnan University; | |
关键词: CRC; UCA1; m6A modification; IGF2BP2; | |
DOI : 10.1186/s12935-021-02288-x | |
来源: DOAJ |
【 摘 要 】
Abstract Background UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC). Methods qRT-PCR was performed to detect the level of UCA1 and IGF2BP2 in CRC samples. CRISPR/Cas9 was employed to knockout (KO) UCA1, METTL3 and WTAP in DLD-1 and HCT-116 cells, while rescue experiments were carried out to re-express METTL3 and WTAP in KO cells. Immunoprecipitation using m6A antibody was performed to determine the m6A modification of UCA1. In vivo pulldown assays using S1m tagging combined with site-direct mutagenesis was carried out to confirm the recognition of m6A-modified UCA1 by IGF2BP2. Cell viability was measured by MTT and colony formation assays. The expression of UCA1 and IGF2BP2 in TCGA CRC database was obtained from GEPIA ( http://gepia.cancer-pku.cn ). Results Our results revealed that IGF2BP2 serves as a reader for m6A modified UCA1 and that adenosine at 1038 of UCA1 is critical to the recognition by IGF2BP2. Importantly, we showed that m6A writers, METTL3 and WTAP positively regulate UCA1 expression. Mechanically, IGF2BP2 increases the stability of m6A-modified UCA1. Clinically, IGF2BP2 is upregulated in CRC tissues compared with normal tissues. Conclusion These results suggest that m6A modification is an important factor contributing to upregulation of UCA1 in CRC tissues.
【 授权许可】
Unknown