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Down-regulation of MTHFD2 inhibits NSCLC progression by suppressing cycle-related genes

Chang Yu1,2, Lehe Yang1, Mengsi Cai1

  • 1Key Laboratory of Heart and Lung, Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Journal of Cellular and Molecular Medicine
|November 29, 2019
PubMed

Insights

Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is overexpressed in non-small cell lung cancer (NSCLC). Inhibiting MTHFD2 reduces NSCLC growth by suppressing cell cycle genes, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial enzyme Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is implicated in various cancers.
  • MTHFD2's role in non-small cell lung cancer (NSCLC) pathogenesis is not well-established.
  • Understanding MTHFD2 expression is crucial for NSCLC research.

Purpose of the Study:

  • To investigate the expression of MTHFD2 in NSCLC.
  • To determine the functional role of MTHFD2 in NSCLC cell growth and tumorigenicity.
  • To elucidate the molecular mechanisms underlying MTHFD2's effect on NSCLC.

Main Methods:

  • Quantitative analysis of MTHFD2 expression in NSCLC tissues and cell lines.
  • In vitro and in vivo experiments involving MTHFD2 knockdown (e.g., using siRNA).
  • Assessment of cell proliferation, colony formation, and tumor growth.
  • Analysis of cell cycle gene expression (mRNA and protein levels) post-MTHFD2 knockdown.

Main Results:

  • MTHFD2 was significantly overexpressed in NSCLC tissues and cell lines.
  • MTHFD2 knockdown suppressed NSCLC cell proliferation and tumorigenicity both in vitro and in vivo.
  • Knockdown of MTHFD2 led to decreased expression of cell cycle genes, including CCNA2, MCM7, and SKP2.
  • These findings suggest MTHFD2 promotes NSCLC development.

Conclusions:

  • MTHFD2 overexpression is a feature of NSCLC.
  • MTHFD2 plays a critical role in promoting NSCLC cell growth and tumorigenicity.
  • The inhibitory effects of MTHFD2 knockdown are mediated through the suppression of cell cycle-related genes.
  • MTHFD2 represents a potential therapeutic target for NSCLC treatment.
Keywords:
bioinformaticscell cyclemethylenetetrahydrofolate dehydrogenase 2non-small cell lung cancer

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