The interaction between PDCD4 and YB1 is critical for cervical cancer stemness and cisplatin resistance

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Cancer multidrug resistance (MDR) is linked to cancer stem cells exhibiting stemness properties.
• The role of Programmed cell death 4 (PDCD4), a proapoptotic gene, in cancer stemness and cisplatin resistance remains unclear.
• PDCD4 expression is reduced in cisplatin-resistant Hela/DDP cells compared to parental Hela cells, with elevated stemness markers.

Purpose of the Study:

• To investigate the role of PDCD4 in cancer stemness and cisplatin resistance.
• To elucidate the molecular mechanisms by which PDCD4 influences multidrug resistance (MDR) and cancer stem cell properties.

Main Methods:

• In vivo xenograft tumor assays and in vitro colony formation and MTT assays were used to assess tumor growth and cell proliferation.
• Western blotting and luciferase reporter assays were employed to analyze protein levels and gene promoter activity.
• Chromatin immunoprecipitation (ChIP), GST-pulldown, and Co-immunoprecipitation (Co-IP) assays were utilized to determine direct protein interactions and binding.

Main Results:

• PDCD4 overexpression inhibited cell proliferation and cisplatin resistance, while PDCD4 deficiency enhanced them.
• PDCD4 decreased pAKT and pYB1 protein levels, leading to reduced MDR1 expression.
• PDCD4 directly binds to YB1, preventing its translocation to the nucleus and subsequent binding to the MDR1 promoter, thereby decreasing MDR1 transcription.

Conclusions:

• PDCD4 plays a crucial role in suppressing cancer stemness and enhancing chemosensitivity.
• The PDCD4-pAKT-pYB1 molecular network regulates MDR1 transcription, impacting stemness-associated cisplatin resistance.
• Targeting the PDCD4-YB1 interaction presents a potential strategy for overcoming multidrug resistance (MDR) in cancer.