Cargando…
LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression
Tumor metastasis is a complex process modulated by both intrinsic and extrinsic factors that ultimately result in poorer patient outcomes, including diminished survival. Pseudogene-derived long non-coding RNAs (lncRNA) play important roles in cancer progression. In the current study, we found that t...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406458/ https://www.ncbi.nlm.nih.gov/pubmed/36010685 http://dx.doi.org/10.3390/cells11162610 |
_version_ | 1784774126072758272 |
---|---|
author | Lin, Yang-Hsiang Liu, Yu-Chin Chen, Cheng-Yi Chi, Hsiang-Cheng Wu, Meng-Han Huang, Po-Shuan Chang, Cheng-Chih Lin, Tzu-Kang Yeh, Chau-Ting Lin, Kwang-Huei |
author_facet | Lin, Yang-Hsiang Liu, Yu-Chin Chen, Cheng-Yi Chi, Hsiang-Cheng Wu, Meng-Han Huang, Po-Shuan Chang, Cheng-Chih Lin, Tzu-Kang Yeh, Chau-Ting Lin, Kwang-Huei |
author_sort | Lin, Yang-Hsiang |
collection | PubMed |
description | Tumor metastasis is a complex process modulated by both intrinsic and extrinsic factors that ultimately result in poorer patient outcomes, including diminished survival. Pseudogene-derived long non-coding RNAs (lncRNA) play important roles in cancer progression. In the current study, we found that the pseudogene-derived lncRNA LPAL2 is downregulated in hepatocellular carcinoma (HCC) tissues, and further showed that elevated LPAL2 expression is positively correlated with survival outcome. The knockdown of LPAL2 in hepatoma cells induced tumor formation, migration, invasion, sphere formation, and drug resistance. Metalloproteinase 9 (MMP9) was identified as an LPAL2-regulated target gene, consistent with clinical findings that LPAL2 expression is significantly associated with MMP9 expression. Furthermore, patients with a higher expression of LPAL2 and lower expression of MMP9 (LPAL2-high/MMP9-low) had a higher survival rate than those with other combinations. Collectively, our findings establish LPAL2 as a novel tumor suppressor in HCC, and suggest targeting LPAL2 and MMP9 as a therapeutic approach for the treatment of HCC. |
format | Online Article Text |
id | pubmed-9406458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94064582022-08-26 LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression Lin, Yang-Hsiang Liu, Yu-Chin Chen, Cheng-Yi Chi, Hsiang-Cheng Wu, Meng-Han Huang, Po-Shuan Chang, Cheng-Chih Lin, Tzu-Kang Yeh, Chau-Ting Lin, Kwang-Huei Cells Article Tumor metastasis is a complex process modulated by both intrinsic and extrinsic factors that ultimately result in poorer patient outcomes, including diminished survival. Pseudogene-derived long non-coding RNAs (lncRNA) play important roles in cancer progression. In the current study, we found that the pseudogene-derived lncRNA LPAL2 is downregulated in hepatocellular carcinoma (HCC) tissues, and further showed that elevated LPAL2 expression is positively correlated with survival outcome. The knockdown of LPAL2 in hepatoma cells induced tumor formation, migration, invasion, sphere formation, and drug resistance. Metalloproteinase 9 (MMP9) was identified as an LPAL2-regulated target gene, consistent with clinical findings that LPAL2 expression is significantly associated with MMP9 expression. Furthermore, patients with a higher expression of LPAL2 and lower expression of MMP9 (LPAL2-high/MMP9-low) had a higher survival rate than those with other combinations. Collectively, our findings establish LPAL2 as a novel tumor suppressor in HCC, and suggest targeting LPAL2 and MMP9 as a therapeutic approach for the treatment of HCC. MDPI 2022-08-22 /pmc/articles/PMC9406458/ /pubmed/36010685 http://dx.doi.org/10.3390/cells11162610 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lin, Yang-Hsiang Liu, Yu-Chin Chen, Cheng-Yi Chi, Hsiang-Cheng Wu, Meng-Han Huang, Po-Shuan Chang, Cheng-Chih Lin, Tzu-Kang Yeh, Chau-Ting Lin, Kwang-Huei LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression |
title | LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression |
title_full | LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression |
title_fullStr | LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression |
title_full_unstemmed | LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression |
title_short | LPAL2 Suppresses Tumor Growth and Metastasis of Hepatocellular Carcinoma by Modulating MMP9 Expression |
title_sort | lpal2 suppresses tumor growth and metastasis of hepatocellular carcinoma by modulating mmp9 expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406458/ https://www.ncbi.nlm.nih.gov/pubmed/36010685 http://dx.doi.org/10.3390/cells11162610 |
work_keys_str_mv | AT linyanghsiang lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT liuyuchin lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT chenchengyi lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT chihsiangcheng lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT wumenghan lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT huangposhuan lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT changchengchih lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT lintzukang lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT yehchauting lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression AT linkwanghuei lpal2suppressestumorgrowthandmetastasisofhepatocellularcarcinomabymodulatingmmp9expression |