Cargando…
A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer
Emerging evidence has proven that long noncoding RNAs (lncRNAs) play important roles in human colorectal cancer (CRC) biology, although few lncRNAs have been characterized in CRC. Therefore, the functional significance of lncRNAs in the malignant progression of CRC still needs to be further explored...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083012/ https://www.ncbi.nlm.nih.gov/pubmed/30092404 http://dx.doi.org/10.1016/j.omtn.2018.06.012 |
_version_ | 1783345895246397440 |
---|---|
author | Lian, Yifan Yan, Changsheng Xu, Hongzhi Yang, Jiebin Yu, Yang Zhou, Jing Shi, Yongguo Ren, Jianlin Ji, Guozhong Wang, Keming |
author_facet | Lian, Yifan Yan, Changsheng Xu, Hongzhi Yang, Jiebin Yu, Yang Zhou, Jing Shi, Yongguo Ren, Jianlin Ji, Guozhong Wang, Keming |
author_sort | Lian, Yifan |
collection | PubMed |
description | Emerging evidence has proven that long noncoding RNAs (lncRNAs) play important roles in human colorectal cancer (CRC) biology, although few lncRNAs have been characterized in CRC. Therefore, the functional significance of lncRNAs in the malignant progression of CRC still needs to be further explored. In this study, through analyzing TCGA RNA sequencing data and other publicly available microarray data, we found a novel lncRNA, LINC00460, whose expression was significantly upregulated in CRC tissues compared to adjacent normal tissues. Consistently, real-time qPCR results also verified that LINC00460 was overexpressed in CRC tissues and cells. Furthermore, high LINC00460 expression levels in CRC specimens were correlated with larger tumor size, advanced tumor stage, lymph node metastasis and shorter overall survival. In vitro and in vivo assays of LINC00460 alterations revealed a complex integrated phenotype affecting cell growth and apoptosis. Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). LINC00460 also functioned as a molecular sponge for miR-149-5p, antagonizing its ability to repress cullin 4A (CUL4A) protein translation. Taken together, our findings support a model in which the LINC00460/EZH2/KLF2 and LINC00460/miR-149-5p/CUL4A crosstalk serve as critical effectors in CRC tumorigenesis and progression, suggesting new therapeutic directions in CRC. |
format | Online Article Text |
id | pubmed-6083012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-60830122018-08-10 A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer Lian, Yifan Yan, Changsheng Xu, Hongzhi Yang, Jiebin Yu, Yang Zhou, Jing Shi, Yongguo Ren, Jianlin Ji, Guozhong Wang, Keming Mol Ther Nucleic Acids Article Emerging evidence has proven that long noncoding RNAs (lncRNAs) play important roles in human colorectal cancer (CRC) biology, although few lncRNAs have been characterized in CRC. Therefore, the functional significance of lncRNAs in the malignant progression of CRC still needs to be further explored. In this study, through analyzing TCGA RNA sequencing data and other publicly available microarray data, we found a novel lncRNA, LINC00460, whose expression was significantly upregulated in CRC tissues compared to adjacent normal tissues. Consistently, real-time qPCR results also verified that LINC00460 was overexpressed in CRC tissues and cells. Furthermore, high LINC00460 expression levels in CRC specimens were correlated with larger tumor size, advanced tumor stage, lymph node metastasis and shorter overall survival. In vitro and in vivo assays of LINC00460 alterations revealed a complex integrated phenotype affecting cell growth and apoptosis. Mechanistically, LINC00460 repressed Krüppel-like factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2). LINC00460 also functioned as a molecular sponge for miR-149-5p, antagonizing its ability to repress cullin 4A (CUL4A) protein translation. Taken together, our findings support a model in which the LINC00460/EZH2/KLF2 and LINC00460/miR-149-5p/CUL4A crosstalk serve as critical effectors in CRC tumorigenesis and progression, suggesting new therapeutic directions in CRC. American Society of Gene & Cell Therapy 2018-07-06 /pmc/articles/PMC6083012/ /pubmed/30092404 http://dx.doi.org/10.1016/j.omtn.2018.06.012 Text en © 2018. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Lian, Yifan Yan, Changsheng Xu, Hongzhi Yang, Jiebin Yu, Yang Zhou, Jing Shi, Yongguo Ren, Jianlin Ji, Guozhong Wang, Keming A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer |
title | A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer |
title_full | A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer |
title_fullStr | A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer |
title_full_unstemmed | A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer |
title_short | A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating KLF2 and CUL4A Expression in Colorectal Cancer |
title_sort | novel lncrna, linc00460, affects cell proliferation and apoptosis by regulating klf2 and cul4a expression in colorectal cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083012/ https://www.ncbi.nlm.nih.gov/pubmed/30092404 http://dx.doi.org/10.1016/j.omtn.2018.06.012 |
work_keys_str_mv | AT lianyifan anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT yanchangsheng anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT xuhongzhi anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT yangjiebin anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT yuyang anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT zhoujing anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT shiyongguo anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT renjianlin anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT jiguozhong anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT wangkeming anovellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT lianyifan novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT yanchangsheng novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT xuhongzhi novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT yangjiebin novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT yuyang novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT zhoujing novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT shiyongguo novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT renjianlin novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT jiguozhong novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer AT wangkeming novellncrnalinc00460affectscellproliferationandapoptosisbyregulatingklf2andcul4aexpressionincolorectalcancer |