MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha

Bharathan Bhavya, H. V. Easwer, G. C. Vilanilam, C. R. Anand, K. Sreelakshmi, Madhusoodanan Urulangodi, P. Rajalakshmi, Issac Neena, C. J. Padmakrishnan, Girish R. Menon, K. Krishnakumar, A. N. Deepti, Srinivas Gopala

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Aims: The study focused on the expression and role of a recent potential cancer therapeutic target protein, MutT Homolog1 (MTH1). MTH1 gets activated in an increased reactive oxygen species (ROS) environment and removes the oxidized nucleotides from the cell. The study aimed to check the role of MTH1 in DNA damage and apoptosis, migration and angiogenesis and also to examine its regulation in glioma. Main methods: The experiments were carried out in human glioma tissue samples and brain tissues of epilepsy patients (non-tumor control). We used two human glioblastomas cell lines, U87MG and U251MG cells. In order to study the role of MTH1 in glioma and to analyze the relation of MTH1 with Hif1α, we have used MTH1 siRNA and Hif1α siRNA respectively. Key findings: We found an increased expression of MTH1 in glioma tissues compared to the non-tumor brain tissues. Correlation analysis revealed that those samples showing reduced expression of MTH1 also had high levels of DNA damage and apoptotic markers, while diminished expression of angiogenesis regulators and levels of migration. MTH1 knockdown in vitro by siRNA in tumor cell lines corroborates the above observation. This justifies the emergence of MTH1 inhibitors as potential first-in-class drugs. Mechanistically, our observations suggest that Hif1α may modulate MTH1 expression. Significance: We found elevated MTH1 expression in glioma irrespective of their grades, while its inhibition affects multiple tumor progression pathways, and that targeting Hif1α could simulate the same.

Original languageEnglish
Article number118673
JournalLife Sciences
Publication statusPublished - 01-01-2021

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)


Dive into the research topics of 'MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha'. Together they form a unique fingerprint.

Cite this