Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression

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) ca...

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Autores principales:	Rong-Zhang He, Jing Jiang, Xinglin Hu, Ming Lei, Jia Li, Weihao Luo, Lili Duan, Zheng Hu, Yin-Yuan Mo, Di-Xian Luo, Wan-Xin Peng
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	CRC UCA1 m6A modification IGF2BP2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/ce9ed89be00042a7ade5a71309b6836c
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spelling	oai:doaj.org-article:ce9ed89be00042a7ade5a71309b6836c2021-11-28T12:36:53ZStabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression10.1186/s12935-021-02288-x1475-2867https://doaj.org/article/ce9ed89be00042a7ade5a71309b6836c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02288-xhttps://doaj.org/toc/1475-2867Abstract 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.Rong-Zhang HeJing JiangXinglin HuMing LeiJia LiWeihao LuoLili DuanZheng HuYin-Yuan MoDi-Xian LuoWan-Xin PengBMCarticleCRCUCA1m6A modificationIGF2BP2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CRC UCA1 m6A modification IGF2BP2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	CRC UCA1 m6A modification IGF2BP2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Rong-Zhang He Jing Jiang Xinglin Hu Ming Lei Jia Li Weihao Luo Lili Duan Zheng Hu Yin-Yuan Mo Di-Xian Luo Wan-Xin Peng Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
description	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.
format	article
author	Rong-Zhang He Jing Jiang Xinglin Hu Ming Lei Jia Li Weihao Luo Lili Duan Zheng Hu Yin-Yuan Mo Di-Xian Luo Wan-Xin Peng
author_facet	Rong-Zhang He Jing Jiang Xinglin Hu Ming Lei Jia Li Weihao Luo Lili Duan Zheng Hu Yin-Yuan Mo Di-Xian Luo Wan-Xin Peng
author_sort	Rong-Zhang He
title	Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
title_short	Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
title_full	Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
title_fullStr	Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
title_full_unstemmed	Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression
title_sort	stabilization of uca1 by n6-methyladenosine rna methylation modification promotes colorectal cancer progression
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ce9ed89be00042a7ade5a71309b6836c
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Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression

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