Cargando…

A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a relatively chemo-resistant tumor. Several multi-kinase inhibitors have been approved for treating advanced HCC. However, most HCC patients are highly refractory to these drugs. Therefore, the development of more effective therapies for advanced HCC patients is urg...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Szu-Jen, Yang, Pei-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145764/
https://www.ncbi.nlm.nih.gov/pubmed/33922244
http://dx.doi.org/10.3390/jpm11050332
_version_ 1783697249554923520
author Wang, Szu-Jen
Yang, Pei-Ming
author_facet Wang, Szu-Jen
Yang, Pei-Ming
author_sort Wang, Szu-Jen
collection PubMed
description Hepatocellular carcinoma (HCC) is a relatively chemo-resistant tumor. Several multi-kinase inhibitors have been approved for treating advanced HCC. However, most HCC patients are highly refractory to these drugs. Therefore, the development of more effective therapies for advanced HCC patients is urgently needed. Stathmin 1 (STMN1) is an oncoprotein that destabilizes microtubules and promotes cancer cell migration and invasion. In this study, cancer genomics data mining identified STMN1 as a prognosis biomarker and a therapeutic target for HCC. Co-expressed gene analysis indicated that STMN1 expression was positively associated with cell-cycle-related gene expression. Chemical sensitivity profiling of HCC cell lines suggested that High-STMN1-expressing HCC cells were the most sensitive to MST-312 (a telomerase inhibitor). Drug–gene connectivity mapping supported that MST-312 reversed the STMN1-co-expressed gene signature (especially BUB1B, MCM2/5/6, and TTK genes). In vitro experiments validated that MST-312 inhibited HCC cell viability and related protein expression (STMN1, BUB1B, and MCM5). In addition, overexpression of STMN1 enhanced the anticancer activity of MST-312 in HCC cells. Therefore, MST-312 can be used for treating STMN1-high expression HCC.
format Online
Article
Text
id pubmed-8145764
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81457642021-05-26 A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma Wang, Szu-Jen Yang, Pei-Ming J Pers Med Article Hepatocellular carcinoma (HCC) is a relatively chemo-resistant tumor. Several multi-kinase inhibitors have been approved for treating advanced HCC. However, most HCC patients are highly refractory to these drugs. Therefore, the development of more effective therapies for advanced HCC patients is urgently needed. Stathmin 1 (STMN1) is an oncoprotein that destabilizes microtubules and promotes cancer cell migration and invasion. In this study, cancer genomics data mining identified STMN1 as a prognosis biomarker and a therapeutic target for HCC. Co-expressed gene analysis indicated that STMN1 expression was positively associated with cell-cycle-related gene expression. Chemical sensitivity profiling of HCC cell lines suggested that High-STMN1-expressing HCC cells were the most sensitive to MST-312 (a telomerase inhibitor). Drug–gene connectivity mapping supported that MST-312 reversed the STMN1-co-expressed gene signature (especially BUB1B, MCM2/5/6, and TTK genes). In vitro experiments validated that MST-312 inhibited HCC cell viability and related protein expression (STMN1, BUB1B, and MCM5). In addition, overexpression of STMN1 enhanced the anticancer activity of MST-312 in HCC cells. Therefore, MST-312 can be used for treating STMN1-high expression HCC. MDPI 2021-04-22 /pmc/articles/PMC8145764/ /pubmed/33922244 http://dx.doi.org/10.3390/jpm11050332 Text en © 2021 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
Wang, Szu-Jen
Yang, Pei-Ming
A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma
title A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma
title_full A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma
title_fullStr A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma
title_full_unstemmed A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma
title_short A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma
title_sort bioinformatics analysis identifies the telomerase inhibitor mst-312 for treating high-stmn1-expressing hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145764/
https://www.ncbi.nlm.nih.gov/pubmed/33922244
http://dx.doi.org/10.3390/jpm11050332
work_keys_str_mv AT wangszujen abioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma
AT yangpeiming abioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma
AT wangszujen bioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma
AT yangpeiming bioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma