YBX1 mediates autophagy by targeting p110β and decreasing the sensitivity to cisplatin in NSCLC

Area of Science:

• Oncology
• Molecular Biology
• Cellular Biology

Background:

• Y-box binding protein 1 (YBX1) is implicated in various cancers.
• The role of YBX1 in autophagy within non-small cell lung cancer (NSCLC) is not well understood.
• Autophagy is a cellular process with complex roles in cancer development and treatment response.

Purpose of the Study:

• To investigate the relationship between YBX1 and autophagy in NSCLC.
• To determine the clinical significance of YBX1 and autophagy markers in NSCLC patients.
• To elucidate the role of YBX1 in regulating sensitivity to cisplatin in NSCLC.

Main Methods:

• Retrospective analysis of NSCLC patient data, correlating YBX1 and autophagy marker (LC3I/II) expression.
• In vitro studies involving knockdown of YBX1 in NSCLC cells to assess effects on autophagy, apoptosis, and cisplatin sensitivity.
• In vivo xenograft tumor model in mice to evaluate the impact of YBX1 overexpression on tumor growth, progression, and cisplatin response.

Main Results:

• YBX1 expression was positively correlated with autophagy in NSCLC.
• Elevated levels of YBX1 and autophagy were observed in NSCLC cells compared to normal bronchial epithelial cells.
• Knockdown of YBX1 suppressed autophagy, enhanced cisplatin sensitivity, and promoted apoptosis in NSCLC cells by inhibiting the p110β/Vps34/beclin1 pathway.
• Overexpression of YBX1 in vivo increased NSCLC growth and reduced cisplatin sensitivity via autophagy induction, associated with increased p110β and beclin1 expression.

Conclusions:

• YBX1 plays a critical role in regulating autophagy in non-small cell lung cancer.
• YBX1-induced autophagy contributes to cisplatin resistance and tumor progression in NSCLC.
• Targeting YBX1 may represent a therapeutic strategy to enhance the efficacy of chemotherapy in NSCLC.