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...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/11/5/332 |
| _version_ | 1797536728099061760 |
|---|---|
| author | Szu-Jen Wang Pei-Ming Yang |
| author_facet | Szu-Jen Wang Pei-Ming Yang |
| author_sort | Szu-Jen Wang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T12:03:57Z |
| format | Article |
| id | doaj.art-99be8a70c1284c918053ebc73b8d2add |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T12:03:57Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-99be8a70c1284c918053ebc73b8d2add2023-11-21T16:42:40ZengMDPI AGJournal of Personalized Medicine2075-44262021-04-0111533210.3390/jpm11050332A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular CarcinomaSzu-Jen Wang0Pei-Ming Yang1Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung 80249, TaiwanGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanHepatocellular 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.https://www.mdpi.com/2075-4426/11/5/332bioinformaticscancer genomicscell cyclehepatocellular carcinomastathmin 1 |
| spellingShingle | Szu-Jen Wang Pei-Ming Yang A Bioinformatics Analysis Identifies the Telomerase Inhibitor MST-312 for Treating High-STMN1-Expressing Hepatocellular Carcinoma Journal of Personalized Medicine bioinformatics cancer genomics cell cycle hepatocellular carcinoma stathmin 1 |
| 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 | bioinformatics cancer genomics cell cycle hepatocellular carcinoma stathmin 1 |
| url | https://www.mdpi.com/2075-4426/11/5/332 |
| work_keys_str_mv | AT szujenwang abioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma AT peimingyang abioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma AT szujenwang bioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma AT peimingyang bioinformaticsanalysisidentifiesthetelomeraseinhibitormst312fortreatinghighstmn1expressinghepatocellularcarcinoma |