FEBS Open Bio (Sep 2023)

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

  • Kengo Tanigawa,
  • Yuya Tomioka,
  • Shunsuke Misono,
  • Shunichi Asai,
  • Naoko Kikkawa,
  • Yoko Hagihara,
  • Takayuki Suetsugu,
  • Hiromasa Inoue,
  • Keiko Mizuno,
  • Naohiko Seki

DOI
https://doi.org/10.1002/2211-5463.13681
Journal volume & issue
Vol. 13, no. 9
pp. 1737 – 1755

Abstract

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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 cell division cycle 7‐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.

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