Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer

Chun Hao Chan, Chia Yu Wu, Navneet Kumar Dubey, Hong Jian Wei, Jui Hua Lu, Samantha Mao, Joy Liang, Yu Hsuan Liang, Hsin Chung Cheng, Win Ping Deng

研究成果: 雜誌貢獻文章同行評審

摘要

Recent reports have indicated the role of highly expressed methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) enzyme in cancers, showing poor survival; however, detailed mechanistic insight of metabolic functions of MTHFD2 have not been well-defined. Therefore, we aimed to examine the metabolic functions and cellular reprograming potential of MTHFD2 in lung cancer (LCa). In this study, we initially confirmed the expression levels of MTHFD2 in LCa not only in tissue and OncomineTM database, but also at molecular levels. Further, we reprogrammed metabolic activities in these cells through MTHFD2 gene knockdown via lentiviral transduction, and assessed their viability, transformation and self-renewal ability. In vivo tumorigenicity was also evaluated in NOD/SCID mice. Results showed that MTHFD2 was highly expressed in stage-dependent LCa tissues as well in cell lines, A549, H1299 and H441. Cellular viability, transformation and self-renewal abilities were significantly inhibited in MTHFD2-knockdown LCa cell lines. These cells also showed suppressed tumor-initiating ability and reduced tumor size compared to vector controls. Under low oxygen tension, MTHFD2-knockdown groups showed no significant increase in sphere formation, and hence the stemness. Conclusively, the suppressed levels of MTHFD2 is essential for cellular metabolic reprogramming leading to inhibited LCa growth and tumor aggressiveness.
原文英語
頁(從 - 到)17930-17947
頁數18
期刊Aging
12
發行號18
DOIs
出版狀態已發佈 - 九月 30 2020

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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