4.6 Article

DNA methylation regulates Microtubule-associated tumor suppressor 1 in human non-small cell lung carcinoma

Journal

EXPERIMENTAL CELL RESEARCH
Volume 374, Issue 2, Pages 323-332

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.12.004

Keywords

Microtubule-associated tumor suppressor 1; DNA methylation; Non-small cell lung carcinoma; DNA methyltransferase

Funding

  1. DST, Govt. of India
  2. SERB-DST, Govt. of India [PDF/2015/000757]
  3. NIT-Rourkela
  4. DBT (Government of India) [BT/PR21318/MED/12/742/2016]

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Microtubule associated tumor suppressor 1 (MTUS1) has been recognized as a tumor suppressor gene in multiple cancers. However, the molecular mechanisms underlying the regulation of MTUS1 are yet to be investigated. This study aimed to clarify the significance of DNA methylation in silencing MTUS1 expression. We report that MTUS1 acts as tumor suppressor in non-small cell lung carcinoma (NSCLC). Analysis of in silica database and subsequent knockdown of DNMT1 suggested an inverse correlation between DNMT1 and mars]. function. Interestingly, increased methylation at MTUS1 promoter is associated with low expression of MTUS1. Treatment with DNA methyltransferases (DNMTs) inhibitor, 5-aza-2'-deoxycytidine (AZA) leads to both reduced promoter methylation accompanied with enrichment of H3K9Ac and enhanced MTUS1 expression. Remarkably, knockdown of MTUS1 showed increased proliferation and migration of NSCLC cells in contrast to diminished proliferation and migration, upon treatment with AZA. We concluded that low expression of MTUS1 correlates to DNA methylation and histone deacetylation in human NSCLC.

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