Oncogene c-Myc promotes epitranscriptome m⁶A reader YTHDF1 expression in colorectal cancer

Area of Science:

• Molecular biology
• Cancer research
• Epigenetics

Background:

• RNA modifications, including N6-methyladenosine (m⁶A), are increasingly recognized for their roles in cancer.
• The YT521-B homology (YTH) domain proteins are key readers of m⁶A modifications.
• The specific role of YTH domain family members in colorectal cancer (CRC) requires further elucidation.

Purpose of the Study:

• To investigate the role of YTH domain family member 1 (YTHDF1) in colorectal cancer progression.
• To explore the transcriptional regulation of YTHDF1 in CRC.
• To assess YTHDF1 as a prognostic biomarker and therapeutic target in CRC.

Main Methods:

• Immunohistochemistry to assess YTHDF1 expression in CRC tissues.
• Correlation analysis of YTHDF1 expression with clinical parameters and patient survival.
• In vitro studies involving YTHDF1 knockdown to evaluate effects on proliferation and drug sensitivity.
• Chromatin immunoprecipitation and gene expression analysis to investigate the upstream regulation of YTHDF1 by c-Myc.

Main Results:

• YTHDF1 expression is significantly associated with advanced tumor depth, lymph node metastasis, and poorer cancer stages.
• High YTHDF1 expression correlates with significantly reduced overall survival in CRC patients, identifying it as an independent prognostic factor.
• Knockdown of YTHDF1 suppressed CRC cell proliferation and increased sensitivity to chemotherapeutic agents like fluorouracil and oxaliplatin.
• The oncogenic transcription factor c-Myc was identified as a key regulator of YTHDF1 expression, forming a c-Myc-YTHDF1 axis.

Conclusions:

• YTHDF1 plays a critical role in the progression of colorectal cancer.
• YTHDF1 serves as a potential prognostic biomarker for CRC.
• The c-Myc-YTHDF1 axis represents a promising therapeutic target for colorectal cancer treatment.