期刊
CELL DEATH & DISEASE
卷 13, 期 2, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41419-021-04497-8
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资金
- National Science Foundation of China [42176096, 42176097]
- Science and Technology Project of Qingdao West Coast New Area [2019-60]
- Traditional Chinese Medicine Scientific Research Project of Qingdao [2020-zyy060]
- Qingdao Outstanding Health Professional Development Fund
- Qilu Health Leading Talent Project
This study reveals that circ-PKD2 plays a role in cisplatin-induced autophagy in oral squamous cell carcinoma cells, and miR-646 plays a critical role in regulating the effects of circ-PKD2 in chemotherapy.
Autophagy is an evolutionally conserved catabolic process that degrades cells to maintain homeostasis. Cisplatin-activated autophagy promotes the expression of circ-PKD2, which plays a role as a tumor suppressor gene in the proliferation, migration, and invasion in oral squamous cell carcinoma (OSCC). However, the role of circ-PKD2 in regulating the sensitivity of OSCC patients to cisplatin remains to be elucidated. Overexpression of circ-PKD2 increased the formation of autophagosomes in OSCC cells and activation of proteins, such as LC3 II/I. Its activation effect on autophagy was, however, alleviated by 3-MA. Bioinformatics analyses and double luciferases reporter assays conducted in this study confirmed the existence of targeted relationships between circ-PKD2 and miR-646 and miR-646 and Atg13. Functional experiments further revealed that miR-646 reversed the autophagy and apoptosis effects of circ-PKD2 in OSCC cells treated with cisplatin. In addition, circ-PKD2 promoted the expression of ATG13 by adsorption of miR-646. Its interference with Atg13 alleviated the activation effects of circ-PKD2 on autophagy and apoptosis of miR-646. Notably, the in vivo animal experiments also confirmed that circ-PKD2 inhibited tumor proliferation and activated autophagy in OSCC cells. This study provides a theoretical basis for using circ-PKD2 as a target to regulate the sensitivity of OSCC patients to cisplatin, thus increasing its chemotherapeutic effects.
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