Cargando…
The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p
Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer and the leading cause of cancer mortality. Several lines of evidence have demonstrated the aberrant expression of long noncoding RNAs (lncRNAs) in carcinogenesis and their universal regulatory properties. A thorough understanding o...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150434/ https://www.ncbi.nlm.nih.gov/pubmed/32278306 http://dx.doi.org/10.1016/j.omtn.2020.03.008 |
_version_ | 1783521028965662720 |
---|---|
author | Lan, Xi Wu, Nan Wu, Litao Qu, Kai Osoro, Ezra Kombo Guan, Dongxian Du, Xiaojuan Wang, Bo Chen, Sifan Miao, Ji Ren, Juan Liu, Li Li, Haiyun Ning, Qilan Li, Dongmin Lu, Shemin |
author_facet | Lan, Xi Wu, Nan Wu, Litao Qu, Kai Osoro, Ezra Kombo Guan, Dongxian Du, Xiaojuan Wang, Bo Chen, Sifan Miao, Ji Ren, Juan Liu, Li Li, Haiyun Ning, Qilan Li, Dongmin Lu, Shemin |
author_sort | Lan, Xi |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer and the leading cause of cancer mortality. Several lines of evidence have demonstrated the aberrant expression of long noncoding RNAs (lncRNAs) in carcinogenesis and their universal regulatory properties. A thorough understanding of lncRNA regulatory roles in HCC pathology would contribute to HCC prevention and treatment. In this study, we identified a novel human lncRNA, LNC-HC, with significantly reduced levels in hepatic tumors from patients with HCC. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide) assays as well as colony formation and wound healing experiments showed that LNC-HC significantly inhibited the proliferation of the HCC cell line Huh7. Xenograft transplantation of LNC-HC-overexpressing Huh7 cells in nude mice resulted in the production of smaller tumors. Mechanistically, LNC-HC inhibited the proliferation of HCC cells by directly interacting with hsa-miR-183-5p. LNC-HC rescued the expression of five tumor suppressors, including AKAP12, DYRK2, FOXN3, FOXO1, and LATS2, that were verified as target genes of hsa-miR-183-5p. Overall, human LNC-HC was identified as a novel tumor suppressor that could inhibit HCC cell proliferation in vitro and suppress tumor growth in vivo by competitively binding hsa-miR-183-5p as a competing endogenous RNA (ceRNA). These findings suggest that LNC-HC could be a biomarker of HCC and provide a novel therapeutic target for HCC treatment. |
format | Online Article Text |
id | pubmed-7150434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-71504342020-04-16 The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p Lan, Xi Wu, Nan Wu, Litao Qu, Kai Osoro, Ezra Kombo Guan, Dongxian Du, Xiaojuan Wang, Bo Chen, Sifan Miao, Ji Ren, Juan Liu, Li Li, Haiyun Ning, Qilan Li, Dongmin Lu, Shemin Mol Ther Nucleic Acids Article Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer and the leading cause of cancer mortality. Several lines of evidence have demonstrated the aberrant expression of long noncoding RNAs (lncRNAs) in carcinogenesis and their universal regulatory properties. A thorough understanding of lncRNA regulatory roles in HCC pathology would contribute to HCC prevention and treatment. In this study, we identified a novel human lncRNA, LNC-HC, with significantly reduced levels in hepatic tumors from patients with HCC. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide) assays as well as colony formation and wound healing experiments showed that LNC-HC significantly inhibited the proliferation of the HCC cell line Huh7. Xenograft transplantation of LNC-HC-overexpressing Huh7 cells in nude mice resulted in the production of smaller tumors. Mechanistically, LNC-HC inhibited the proliferation of HCC cells by directly interacting with hsa-miR-183-5p. LNC-HC rescued the expression of five tumor suppressors, including AKAP12, DYRK2, FOXN3, FOXO1, and LATS2, that were verified as target genes of hsa-miR-183-5p. Overall, human LNC-HC was identified as a novel tumor suppressor that could inhibit HCC cell proliferation in vitro and suppress tumor growth in vivo by competitively binding hsa-miR-183-5p as a competing endogenous RNA (ceRNA). These findings suggest that LNC-HC could be a biomarker of HCC and provide a novel therapeutic target for HCC treatment. American Society of Gene & Cell Therapy 2020-03-20 /pmc/articles/PMC7150434/ /pubmed/32278306 http://dx.doi.org/10.1016/j.omtn.2020.03.008 Text en © 2020 The Author(s) 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 Lan, Xi Wu, Nan Wu, Litao Qu, Kai Osoro, Ezra Kombo Guan, Dongxian Du, Xiaojuan Wang, Bo Chen, Sifan Miao, Ji Ren, Juan Liu, Li Li, Haiyun Ning, Qilan Li, Dongmin Lu, Shemin The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p |
title | The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p |
title_full | The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p |
title_fullStr | The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p |
title_full_unstemmed | The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p |
title_short | The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p |
title_sort | human novel gene lnc-hc inhibits hepatocellular carcinoma cell proliferation by sequestering hsa-mir-183-5p |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150434/ https://www.ncbi.nlm.nih.gov/pubmed/32278306 http://dx.doi.org/10.1016/j.omtn.2020.03.008 |
work_keys_str_mv | AT lanxi thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT wunan thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT wulitao thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT qukai thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT osoroezrakombo thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT guandongxian thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT duxiaojuan thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT wangbo thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT chensifan thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT miaoji thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT renjuan thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT liuli thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lihaiyun thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT ningqilan thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lidongmin thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lushemin thehumannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lanxi humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT wunan humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT wulitao humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT qukai humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT osoroezrakombo humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT guandongxian humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT duxiaojuan humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT wangbo humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT chensifan humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT miaoji humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT renjuan humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT liuli humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lihaiyun humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT ningqilan humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lidongmin humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p AT lushemin humannovelgenelnchcinhibitshepatocellularcarcinomacellproliferationbysequesteringhsamir1835p |