Cargando…
LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia
Uncontrolled proliferation is the hallmark of cancer cells. Previous studies mainly focused on the role of protein-coding genes in cancer cell proliferation. Emerging evidence showed that long non-coding RNAs (lncRNAs) also play critical roles in cancer cell proliferation and growth. LncRNA KCNQ1OT1...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371007/ https://www.ncbi.nlm.nih.gov/pubmed/34404765 http://dx.doi.org/10.1038/s41419-021-04080-1 |
_version_ | 1783739552462012416 |
---|---|
author | Tang, Doudou Luo, Yujiao Jiang, Yafeng Hu, Piao Peng, Hongling Wu, Shangjie Zhang, Guangsen Wang, Yewei |
author_facet | Tang, Doudou Luo, Yujiao Jiang, Yafeng Hu, Piao Peng, Hongling Wu, Shangjie Zhang, Guangsen Wang, Yewei |
author_sort | Tang, Doudou |
collection | PubMed |
description | Uncontrolled proliferation is the hallmark of cancer cells. Previous studies mainly focused on the role of protein-coding genes in cancer cell proliferation. Emerging evidence showed that long non-coding RNAs (lncRNAs) also play critical roles in cancer cell proliferation and growth. LncRNA KCNQ1OT1 is found to contribute to carcinogenesis, but its role in acute promyelocytic leukemia (APL) is unclear. In this study, by analyzing data from Gene Expression Omnibus, The Cancer Genome Atlas database and our clinical samples, we found that KCNQ1OT1 was selectively highly expressed in APL. Functional assays demonstrated that knockdown of KCNQ1OT1 reduced APL cell proliferation and increased apoptosis. Further evidence showed that KCNQ1OT1 was mainly located in the cytoplasm of APL patient-derived NB4 cells and APL patient bone marrow samples. Mechanistically, KCNQ1OT1 bound to RNA binding protein FUS, and silencing either KCNQ1OT1 or FUS reduced the expression level and stability of MAP3K1 mRNA. Whereas KCNQ1OT1 and FUS did not affect each other. Importantly, knockdown of MAP3K1 impaired APL cell proliferation. Finally, c-Myc transactivated KCNQ1OT1 in APL cells through binding to its promoter while knockdown of c-Myc decreased KCNQ1OT1 expression. Our results not only revealed that c-Myc transactivated KCNQ1OT1 and upregulated KCNQ1OT1 promoted APL cell proliferation, but also demonstrated that KCNQ1OT1 bound to FUS to synergistically stabilize MAP3K1 mRNA, thus facilitating APL cell proliferation. This study established a previously unidentified role of KCNQ1OT1 in the development of APL, and KCNQ1OT1 may serve as a potential therapeutic target for APL. |
format | Online Article Text |
id | pubmed-8371007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83710072021-09-02 LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia Tang, Doudou Luo, Yujiao Jiang, Yafeng Hu, Piao Peng, Hongling Wu, Shangjie Zhang, Guangsen Wang, Yewei Cell Death Dis Article Uncontrolled proliferation is the hallmark of cancer cells. Previous studies mainly focused on the role of protein-coding genes in cancer cell proliferation. Emerging evidence showed that long non-coding RNAs (lncRNAs) also play critical roles in cancer cell proliferation and growth. LncRNA KCNQ1OT1 is found to contribute to carcinogenesis, but its role in acute promyelocytic leukemia (APL) is unclear. In this study, by analyzing data from Gene Expression Omnibus, The Cancer Genome Atlas database and our clinical samples, we found that KCNQ1OT1 was selectively highly expressed in APL. Functional assays demonstrated that knockdown of KCNQ1OT1 reduced APL cell proliferation and increased apoptosis. Further evidence showed that KCNQ1OT1 was mainly located in the cytoplasm of APL patient-derived NB4 cells and APL patient bone marrow samples. Mechanistically, KCNQ1OT1 bound to RNA binding protein FUS, and silencing either KCNQ1OT1 or FUS reduced the expression level and stability of MAP3K1 mRNA. Whereas KCNQ1OT1 and FUS did not affect each other. Importantly, knockdown of MAP3K1 impaired APL cell proliferation. Finally, c-Myc transactivated KCNQ1OT1 in APL cells through binding to its promoter while knockdown of c-Myc decreased KCNQ1OT1 expression. Our results not only revealed that c-Myc transactivated KCNQ1OT1 and upregulated KCNQ1OT1 promoted APL cell proliferation, but also demonstrated that KCNQ1OT1 bound to FUS to synergistically stabilize MAP3K1 mRNA, thus facilitating APL cell proliferation. This study established a previously unidentified role of KCNQ1OT1 in the development of APL, and KCNQ1OT1 may serve as a potential therapeutic target for APL. Nature Publishing Group UK 2021-08-17 /pmc/articles/PMC8371007/ /pubmed/34404765 http://dx.doi.org/10.1038/s41419-021-04080-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tang, Doudou Luo, Yujiao Jiang, Yafeng Hu, Piao Peng, Hongling Wu, Shangjie Zhang, Guangsen Wang, Yewei LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
title | LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
title_full | LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
title_fullStr | LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
title_full_unstemmed | LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
title_short | LncRNA KCNQ1OT1 activated by c-Myc promotes cell proliferation via interacting with FUS to stabilize MAP3K1 in acute promyelocytic leukemia |
title_sort | lncrna kcnq1ot1 activated by c-myc promotes cell proliferation via interacting with fus to stabilize map3k1 in acute promyelocytic leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371007/ https://www.ncbi.nlm.nih.gov/pubmed/34404765 http://dx.doi.org/10.1038/s41419-021-04080-1 |
work_keys_str_mv | AT tangdoudou lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT luoyujiao lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT jiangyafeng lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT hupiao lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT penghongling lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT wushangjie lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT zhangguangsen lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia AT wangyewei lncrnakcnq1ot1activatedbycmycpromotescellproliferationviainteractingwithfustostabilizemap3k1inacutepromyelocyticleukemia |