Minichromosome maintenance proteins in lung adenocarcinoma: clinical significance and therapeutic targets

  • FEBS Open Bio. 2023 Jul 30. doi: 10.1002/2211-5463.13681.
Kengo Tanigawa  1 ,  Yuya Tomioka  1 ,  Shunsuke Misono  1 ,  Shunichi Asai  2 ,  Naoko Kikkawa  2 ,  Yoko Hagihara  1 ,  Takayuki Suetsugu  1 ,  Hiromasa Inoue  1 ,  Keiko Mizuno  1 ,  Naohiko Seki  2
Affiliations
  • 1. Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan.
  • 2. Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, 260-8670, Japan.
PMID: 37517032 DOI: 10.1002/2211-5463.13681
Abstract

Lung Cancer is the most common cause of cancer-related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2-MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression of MCM4 (p = 0.0032), MCM5 (p = 0.0032), and MCM7 (p = 0.0110) significantly predicted 5-year survival rates in patients with LUAD. Simurosertib (TAK-931) significantly suppressed the proliferation of LUAD cells by inhibiting CDC7-mediated MCM2 phosphorylation. This finding suggested that MCM2 might be a therapeutic target for LUAD. Moreover, analysis of the epigenetic regulation of MCM2 showed that miR-139-3p, miR-378a-5p, and miR-2110 modulated MCM2 expression in LUAD cells. In patients with LUAD, understanding the role of these miRNAs may improve prognoses.

Keywords
MCM; lung adenocarcinoma; miR-139-3p; miR-2110; miR-378a-5p; simurosertib.
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