A bioinformatics analysis identifies the telomerase inhibitor mst-312 for treating high-stmn1-expressing hepatocellular carcinoma

Szu Jen Wang, Pei Ming Yang

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number332
JournalJournal of Personalized Medicine
Volume11
Issue number5
DOIs
Publication statusPublished - 2021

Keywords

  • Bioinformatics
  • Cancer genomics
  • Cell cycle
  • Hepatocellular carcinoma
  • Stathmin 1

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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