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MTHFD1L knockdown diminished cells growth in papillary thyroid cancer
Dandan Yi1, Yiminu'er Yilihamu1, Chaoyu Jiang2
1Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Tissue & Cell
|July 23, 2022
Summary
Methylenetetrahydrofolate dehydrogenase (MTHFD1L) is elevated in papillary thyroid cancer (PTC). Inhibiting MTHFD1L reduces tumor growth and increases apoptosis, suggesting it as a therapeutic target for PTC.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like (MTHFD1L) is a mitochondrial enzyme crucial for tetrahydrofolate synthesis.
- Dysregulation of folate metabolism is implicated in various cancers, including thyroid cancer.
Purpose of the Study:
- To investigate the role and therapeutic potential of MTHFD1L in papillary thyroid cancer (PTC).
- To determine the impact of MTHFD1L expression on PTC cell proliferation, apoptosis, and related signaling pathways.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and analysis of The Cancer Genome Atlas (TCGA) database to assess MTHFD1L expression.
- In vitro and in vivo experiments involving MTHFD1L knockdown using lentivirus and CRISPR-Cas9 systems.
- Gene expression profiling (Affymetrix Genechip), western blotting, and flow cytometry to evaluate cellular effects and molecular mechanisms.
Main Results:
- MTHFD1L mRNA and protein levels were significantly upregulated in PTC tissues and cell lines compared to normal tissues.
- MTHFD1L knockdown suppressed PTC cell growth, induced apoptosis, and inhibited tumor growth in vivo.
- Knockdown of MTHFD1L led to decreased expression of key proteins involved in cell cycle progression and survival, including CCND1, Notch2, Hes1, Bcl-2, and PCNA, while increasing Bax expression.
Conclusions:
- MTHFD1L plays a significant role in promoting PTC cell proliferation and survival.
- Targeting MTHFD1L through knockdown effectively inhibits PTC progression.
- MTHFD1L represents a promising therapeutic target for the treatment of papillary thyroid cancer.
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