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Long noncoding RNA UCA1 promotes the expression and function of P-glycoprotein by sponging miR-16-5p in human placental BeWo cells

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机构: [1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, China. [2]Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China. [3]The major of MSc Cancer, Cancer Institute of University College London, London, UK. [4]West China Medical School of Sichuan University, Chengdu, China. [5]The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China. [6]Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China. [7]Key Laboratory of Development and Diseases of Women and Children of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, China.
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关键词: ABCB1 long noncoding RNA UCA1 miR-16-5p P-glycoprotein placenta

摘要:
Investigations on placental P-glycoprotein (P-gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P-gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P-gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P-gp expression and its cellular efflux function, respectively. RNA-FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR-16-5p was screened out. Thereafter, we confirmed that miR-16-5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P-gp expression and its cellular efflux function was enhanced or reduced after miR-16-5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR-16-5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P-gp. Lastly, dual-luciferase reporter system, RNA-binding protein immunoprecipitation and RNA pull-down assays were performed to explore the relationships among lncRNA UCA1, miR-16-5p, and ABCB1. It was found that lncRNA UCA1(1103-1125) could directly interact with miR-16-5p and miR-16-5p could directly target ABCB1 coding DNA sequence region (882-907). In conclusion, LncRNA UCA1 could promote the expression and function of P-gp by sponging miR-16-5p in BeWo cells.© 2022 Federation of American Societies for Experimental Biology.

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出版当年[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 生物学 3 区 细胞生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 生物学 3 区 细胞生物学
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第一作者机构: [1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, China. [2]Department of Pediatric Cardiology, Children's Hospital of Soochow University, Suzhou, China.
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通讯作者:
通讯机构: [1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, Chengdu, China. [5]The Cardiac Development and Early Intervention Unit, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, China. [*1]Department of Pediatric Cardiology, West China Second University Hospital, Sichuan University, No. 20, Section 3, South Renmin Road, Chengdu, Sichuan 610041, China.
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