Exosomal miR-21-5p derived from cisplatin-resistant SKOV3 ovarian cancer cells promotes glycolysis and inhibits chemosensitivity of its progenitor SKOV3 cells by targeting PDHA1.

Abstract

Ovarian cancer (OC) is a common reason for gynecologic cancer death. Standard treatments of OC consist of surgery and chemotherapy. However, chemoresistance should be considered. Exosomal miR-21-5p has been shown to regulate the chemosensitivity of cancer cells through regulating pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1). However, the role of miR-21-5p/PDHA1 in OC is unclear. The levels of miR-21-5p and PDHA1 in clinical samples and cells were investigated. Exosomes derived from SKOV3/cisplatin (SKOV3/DDP) cells (DDP-Exos) were isolated and used to treat SKOV3 cells to test DDP-Exos effects on SKOV3 cells. Extracellular acidification rate and oxygen consumption rate were tested with a Seahorse analyzer. Cell apoptosis was analyzed by a flow cytometer. PDHA1 was overexpressed and miR-21-5p was silenced in SKOV3 cells to study the underlying mechanism of miR-21-5p in OC. Quantitative real-time PCR and immunoblots were applied to measure gene expression at mRNA and protein levels. The levels of PDHA1 in DDP-resistant SKOV3 or tumor tissues were significantly decreased while the levels of miR-21-5p were remarkably upregulated. miR-21-5p in DDP-Exos was sharply increased compared to that of Exos. Data also indicated that DDP-Exos treatment suppressed the sensitivity of SKOV3 cells to DDP and promoted cell viability and glycolysis of SKOV3 cells through inhibiting PDHA1 by exosomal miR-21-5p. miR-21-5p derived from DDP-resistant SKOV3 OC cells promotes glycolysis and inhibits chemosensitivity of its progenitor SKOV3 cells by targeting PDHA1. Our data highlights the important role of miR-21-5p/PDHA1 axis in OC and sheds light on new therapeutic development.

• Authors: Liangwu Zhuang, Binbin Zhang, Xiaomei Liu, Lan Lin, Lingli Wang, Zhejing Hong, Jie Chen
• Journal: Cell biology international (Cell Biol Int) Vol. 45 Issue 10 Pg. 2140-2149 (Oct 2021) ISSN: 1095-8355 [Electronic] England
• PMID: 34288231 (Publication Type: Journal Article)
• Copyright: © 2021 International Federation for Cell Biology.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• MIRN21 microRNA, human
• MicroRNAs
• Pyruvate Dehydrogenase (Lipoamide)
• pyruvate dehydrogenase E1alpha subunit
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Exosomes (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Glycolysis
• Humans
• MicroRNAs (genetics)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, pathology)
• Prognosis
• Pyruvate Dehydrogenase (Lipoamide) (genetics, metabolism)
• Tumor Cells, Cultured