Jing Zhang1, Jinyu Liu2, Xinyan Xu1, Li Li3. 1. The 1st Department of Gynecological Surgery, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830011, China. 2. The 1st Department of Gynecological Cancer, Jilin Provincial Cancer Hospital, Changchun, 130012, China. 3. The 1st Department of Gynecological Surgery, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, 830011, China. jzhang1982@outlook.com.
Abstract
PURPOSE: To investigate how curcumin alters the extracellular vesicles' (EVs) capability to ship drug resistance in ovarian cancer. METHODS: The EVs from cisplatin-resistant A2780cp cells with curcumin treatment (EVs-CU) or without curcumin treatment (EVs-N) were collected for lncRNA profiling. Curcumin's effect on MEG3 promoter methylation and MEG3 expression were studied by MSP and qRT-PCR, respectively. The regulative effect of MEG3 on miR-214 expression and the functional role of EVs mediated transfer of miR-214 in cisplatin resistance were further investigated. RESULTS: Curcumin weakened the EVs-N's capability to induce drug resistance and induced significant changes of lncRNAs in the EVs. MEG3 is one of the most upregulated lncRNAs. Curcumin led to demethylation in the promoter region of MEG3 and 5-AZA-dC treatment restored MEG3 expression in a dose dependent manner. There were at least two binding sites between MEG3 and miR-214. MEG3 restoration by curcumin significantly reduced miR-214 in cells and in EVs. Functionally, miR-214 inhibition weakened the EVs-N's capability to enhance chemoresistance, while miR-214 overexpression increased the capability of EVs-CU in inducing chemoresistance. CONCLUSION: Curcumin can restore MEG3 levels via demethylation. MEG3 upregulation can decrease EVs mediated transfer of miR-214 in ovarian cancer cells, thereby reducing drug resistance.
PURPOSE: To investigate how curcumin alters the extracellular vesicles' (EVs) capability to ship drug resistance in ovarian cancer. METHODS: The EVs from cisplatin-resistant A2780cp cells with curcumin treatment (EVs-CU) or without curcumin treatment (EVs-N) were collected for lncRNA profiling. Curcumin's effect on MEG3 promoter methylation and MEG3 expression were studied by MSP and qRT-PCR, respectively. The regulative effect of MEG3 on miR-214 expression and the functional role of EVs mediated transfer of miR-214 in cisplatin resistance were further investigated. RESULTS:Curcumin weakened the EVs-N's capability to induce drug resistance and induced significant changes of lncRNAs in the EVs. MEG3 is one of the most upregulated lncRNAs. Curcumin led to demethylation in the promoter region of MEG3 and 5-AZA-dC treatment restored MEG3 expression in a dose dependent manner. There were at least two binding sites between MEG3 and miR-214. MEG3 restoration by curcumin significantly reduced miR-214 in cells and in EVs. Functionally, miR-214 inhibition weakened the EVs-N's capability to enhance chemoresistance, while miR-214 overexpression increased the capability of EVs-CU in inducing chemoresistance. CONCLUSION:Curcumin can restore MEG3 levels via demethylation. MEG3 upregulation can decrease EVs mediated transfer of miR-214 in ovarian cancer cells, thereby reducing drug resistance.
Entities:
Keywords:
Cisplatin resistance; Curcumin; Extracellular vesicles; MEG3; MiR-214; Ovarian cancer
Authors: Priya Samuel; Laura Ann Mulcahy; Fiona Furlong; Helen O McCarthy; Susan Ann Brooks; Muller Fabbri; Ryan Charles Pink; David Raul Francisco Carter Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-01-05 Impact factor: 6.237
Authors: Monal Patel; Yinu Wang; Elizabeth T Bartom; Rohin Dhir; Kenneth P Nephew; Daniela Matei; Andrea E Murmann; Ernst Lengyel; Marcus E Peter Journal: Cancer Res Date: 2021-06-15 Impact factor: 12.701