Cancer Management and Research (Jan 2021)
LncRNA UCA1 Enhances Cisplatin Resistance by Regulating CYP1B1-mediated Apoptosis via miR-513a-3p in Human Gastric Cancer
Abstract
Haidong Cheng,1,* Gaowa Sharen,2,* Zhaoyang Wang,1 Jing Zhou3 1Department of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, People’s Republic of China; 2Department of Pathological Anatomy, College of Basic Medicine of Inner Mongolia Medical University, Hohhot 010059, People’s Republic of China; 3Department of Pharmacology, College of Basic Medicine of Inner Mongolia Medical University, Hohhot 010059, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaoyang WangDepartment of Gastroenterology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, People’s Republic of ChinaEmail [email protected] ZhouDepartment of Pharmacology, College of Basic Medicine of Inner Mongolia Medical University, Hohhot 010059, People’s Republic of ChinaEmail [email protected]: Chemoresistance contributes to treatment failure of gastric cancer (GC) patients but the molecular mechanism of chemoresistance in GC is still unclear. Long-chain noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is associated with resistance to chemotherapy drugs.Methods: We detected the expression of UCA1 in 53 pairs of GC tumor tissue and adjacent normal tissue, human normal gastric mucosa cells (GES-1) and human GC cells (HGC-27, SNU-5, AGS, SGC-7901, and NCI-N87) using RT-qPCR. Small RNA interference technology was used to knock down the expression of UCA1 in gastric cancer cells. CCK8 solution was used to detect cell viability. Flow cytometry was used to detect apoptosis, and Western blotting was used to detect protein expression.Results: UCA1 was highly expressed in GC tissues and cells, and knockdown of UCA1 increased chemosensitivity to cisplatin by inducing cell apoptosis. Furthermore, UCA1 promoted CYP1B1 expression by binding to miR-513a-3p in human GC cells in vitro, and UCA1/CYP1B1 expression was negatively related to miR-513a-3p expression, while UCA1 expression was positively related to CYP1B1 expression in human GC tissues. Moreover, overexpression of miR-513a-3p or knockdown of CYP1B1 increased chemosensitivity to cisplatin, and knockdown of miR-513a-3p or overexpression of CYP1B1 decreased chemosensitivity to cisplatin by inducing cell apoptosis in human GC cells. Importantly, overexpression of CYP1B1 reduced chemosensitivity to cisplatin which increased by knockdown of UCA1, and knockdown of CYP1B1 increased chemosensitivity to cisplatin which decreased by knockdown of miR-513a-3p in human GC cells.Conclusion: The lncRNA UCA1/miR-513a-3p/CYP1B1 axis regulates cisplatin resistance in human GC cells; hence, it is a potential target for treating chemoresistance in GC.Keywords: gastric cancer, urothelial cancer associated 1, chemoresistance
