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

• Published in: The FASEB journal Vol. 37; no. 1; p. e22657
• Main Authors: Tang, Changqing, Deng, Yuxin, Shao, Shuran, Guo, Yafei, Yang, Lixia, Yan, Yu, Zhang, Yi, Qiu, Dajian, Zhou, Kaiyu, Hua, Yimin, Wang, Chuan
• Format: Journal Article
• Language: English
• Published: United States 01.01.2023
• Subjects: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Transitional Cell; Female; Humans; MicroRNAs - genetics; Placenta; Pregnancy; RNA, Long Noncoding - genetics; RNA, Messenger; Urinary Bladder Neoplasms; P-glycoprotein; placenta; ABCB1; long noncoding RNA UCA1; miR-16-5p
• ISSN: 1530-6860
• DOI: 10.1096/fj.202201051R

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.