OncoTargets and Therapy (Apr 2020)
LncRNA HOTTIP Participates in Cisplatin Resistance of Tumor Cells by Regulating miR-137 Expression in Pancreatic Cancer
Abstract
Feng Yin,1 Qian Zhang,2 Zhihui Dong,3 Jie Hu,3 Zhiqiang Ma4 1Department of Pharmacy, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People’s Republic of China; 2Thyroid and Mammary Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People’s Republic of China; 3Imaging Department, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, People’s Republic of China; 4Department of Gastroenterology, Second Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, People’s Republic of ChinaCorrespondence: Feng YinDepartment of Pharmacy, Luoyang Central Hospital Affiliated to Zhengzhou University, 288 Zhongzhou Middle Road, Luoyang 471000, People’s Republic of ChinaTel +86-18638482767Email [email protected]: This study aimed to investigate the effect of HOTTIP and miR-137 on cisplatin resistance of pancreatic cancer cells, and study the mechanism of the effect of HOTTIP on the resistance to cisplatin in pancreatic cancer cells, so as to provide new targets for clinical treatment of pancreatic cancer.Methods: Pancreatic cancer cells were induced to be resistant to cisplatin by gradually increasing cisplatin concentration at a low concentration gradient in vitro. The changes of HOTTIP and miR-137 were detected, and the effects of HOTTIP and miR-137 on cisplatin efficacy of pancreatic cancer cisplatin-resistant cells were analyzed to explore the mechanism of HOTTIP on cisplatin resistance of pancreatic cancer cells.Results: After inducing cisplatin resistance in pancreatic cancer cells, the expression level of HOTTIP in pancreatic cancer cells further increased and miR-137 decreased. Silencing HOTTIP or over-expression of miR-137 can increase the sensitivity of pancreatic cancer cisplatin-resistant cells to cisplatin, inhibit the proliferation of pancreatic cancer cells, and promote apoptosis. And we found HOTTIP can target to inhibit miR-137 expression. Rescue experiments showed that regulating miR-137 cannot affect the expression of HOTTIP, miR-137 is a downstream target of HOTTIP, and down-regulation of miR-137 expression can obviously hinder the cisplatin sensitization effect of silencing HOTTIP on cisplatin-resistant pancreatic cancer cells.Conclusion: Silencing HOTTIP reverses cisplatin resistance of pancreatic cancer cells by promoting miR-137 expression.Keywords: IncRNA HOTTIP, miR-137, pancreatic cancer, cisplatin, drug resistance, targeted therapy
