Long noncoding RNA ZEB1-AS1 affects paclitaxel and cisplatin resistance by regulating MMP19 in epithelial ovarian cancer
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GYNECOLOGIC ONCOLOGY
Long noncoding RNA ZEB1‑AS1 affects paclitaxel and cisplatin resistance by regulating MMP19 in epithelial ovarian cancer cells Chencheng Dai1,2 · Pengfei Xu1 · Siyu Liu1,2 · Sujuan Xu3 · Juan Xu1,2 · Ziyi Fu1 · Jian Cao2 · Mingming Lv1 · Juan Zhou2 · Guangquan Liu1,2 · Huilin Zhang2 · Xuemei Jia2 Received: 7 May 2020 / Accepted: 21 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose The long noncoding RNA (lncRNA) ZEB1-AS1 is reported overexpressed in sensitive ovarian cancer cells A2780 compared with paclitaxel (PTX)—and cisplatin (DDP)- resistant. However, the function and mechanism of ZEB1-AS1 in EOC cells still unknown. Methods We used quantitative real-time PCR (qPCR) to detect ZEB1-AS1 expression in A2780 and A2780/R cells. A combination of siRNA, plasmids, CCK8 and flow cytometry was used to detect the effect of ZEB1-AS1 on ovarian cancer cell A2780 PTX and DDP resistance. Transcriptome sequencing, qPCR, and western blot were used for further mechanistic studies. Results ZEB1-AS1 depletion using siRNA in chemosensitive A2780 cells significantly increased PTX and DDP resistance. In contrast, ZEB1-AS1 overexpression in PTX- and DDP-resistant A2780/resistant (A2780/R) cells reversed the observed drug resistance. Thus, ZEB1-AS1 plays an important role in PTX and DDP resistance in EOC cells. However, quantitative real-time PCR (qPCR) and western blot results suggested that ZEB1-AS1 did not regulate chemoresistance through regulation of ZEB1 protein. We used sequencing to detect mRNA expression changes in A2780 cells after ZEB1-AS1 silencing. The results indicated that MMP19 was the likely downstream factor of ZEB1-AS1. We further examined whether ZEB1-AS1 played an important role in chemoresistance by silencing MMP19 in ZEB1-AS1-overexpressing cells. CCK8 assay results suggested that MMP19 knockdown promoted ZEB1-AS1-induced chemoresistance to PTX and DDP in A2780 cells. Conclusion This study is the first to reveal that ZEB1-AS1 plays a pivotal role in cancer chemoresistance. Keywords ZEB1-AS1 · Epithelial ovarian cancer · Chemoresistance · MMP19
Introduction Chencheng Dai, Pengfei Xu and Siyu Liu contributed equally to this work and are the joint first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00404-020-05858-y) contains supplementary material, which is available to authorized users. * Xuemei Jia [email protected] 1
Nanjing Maternal and Child Health Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China
2
Department of Gynecology, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China
3
Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 210004, China
Epithelial ovarian cancer (EOC) is one of the most common gynecological malignancies
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