The m6 RNA methylation regulator KIAA1429 is associated with autophagy-mediated drug resistance in lung cancer.
Bo MaLei XiuLili DingPublished in: FASEB bioAdvances (2024)
N6-methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification-mediated autophagy underlying non-small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib-resistant cells (PC9-GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3' untranslated regions (3'-UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.
Keyphrases
- small cell lung cancer
- advanced non small cell lung cancer
- cell death
- epidermal growth factor receptor
- brain metastases
- endoplasmic reticulum stress
- induced apoptosis
- signaling pathway
- oxidative stress
- end stage renal disease
- cell cycle arrest
- newly diagnosed
- ejection fraction
- poor prognosis
- papillary thyroid
- gene expression
- prognostic factors
- squamous cell carcinoma
- patient reported outcomes
- squamous cell
- genome wide
- cell proliferation
- cancer therapy
- lymph node metastasis