CAPRIN1/TYMS/MTHFD2 axis promotes EMT process in nasopharyngeal carcinoma development.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Nasopharyngeal carcinoma (NPC) is a malignancy often leading to treatment failure due to metastasis, frequently driven by epithelial-mesenchymal transition (EMT).
• The precise role and regulatory mechanisms of thymidylate synthetase (TYMS) in NPC's EMT process remain largely undetermined.
• Understanding TYMS's upstream and downstream interactions is crucial for developing effective NPC therapies.

Purpose of the Study:

• To elucidate the role of thymidylate synthetase (TYMS) in the epithelial-mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC).
• To investigate the upstream and downstream regulatory mechanisms of TYMS in NPC metastasis.
• To identify potential therapeutic targets within the TYMS regulatory network for NPC.

Main Methods:

• Utilized NPC cell lines (HK-1, C666-1) with TYMS knockdown and overexpression via lentivirus.
• Assessed cell migration and invasion using wound-healing and Transwell assays.
• Employed RNA immunoprecipitation and RNA-sequencing to explore protein-mRNA interactions and downstream regulatory pathways.

Main Results:

• TYMS expression was significantly elevated in NPC tissues.
• TYMS modulation directly impacted EMT processes, with silencing inhibiting and overexpression promoting EMT, evidenced by changes in E-cadherin, Slug, MMP2, and MMP9.
• Identified CAPRIN1 as a TYMS mRNA-binding protein that promotes EMT, and MTHFD2 as a downstream effector regulated by TYMS, both critical in NPC progression.

Conclusions:

• The CAPRIN1/TYMS/MTHFD2 axis is a key driver of EMT and metastasis in NPC.
• This axis represents a promising therapeutic target for NPC treatment and adjuvant therapy.
• Further research into this pathway could lead to novel strategies for overcoming treatment resistance in NPC.