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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
Author(s) -
Zhuang Liangwu,
Zhang Binbin,
Liu Xiaomei,
Lin Lan,
Wang Lingli,
Hong Zhejing,
Chen Jie
Publication year - 2021
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11671
Subject(s) - cisplatin , apoptosis , ovarian cancer , microvesicles , cancer cell , progenitor cell , cancer research , chemistry , viability assay , microrna , biology , microbiology and biotechnology , stem cell , medicine , cancer , chemotherapy , biochemistry , gene
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.