Zhi-Qiang Gao1, Jun-Feng Wang2, De-Hua Chen2, Xue-Song Ma2, Wu Yang2, Tang Zhe2, Xiao-Wei Dang2. 1. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: drgaozhiqiang@163.com. 2. Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Abstract
OBJECTIVE: To explore the core mechanism of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the regulation of multidrug resistance of pancreatic cancer cells. METHODS: mRNA levels of GAS5, miR-181c-5p and Hippo pathway related genes were detected by quantitative real-time PCR (qRT-PCR). Protein levels of MDR-1, MST1, YAP and TAZ were measured by western blot. Cell viability was detected by MTT assay. The combination between GAS5 and miR-181c-5p was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assay. We also established pancreatic cancer-bearing mice model and analyzed tumor volumes. RESULTS: Our data showed GAS5 expression was significantly down-regulated, miR-181c-5p expression was significantly up-regulated in pancreatic cancer cells. Besides, Overexpresson of GAS5 obviously inhibited cell viability, while GAS5 knockdown showed the opposite outcome. Additionally, we also found that GAS5 negatively regulated miR-181c-5p, and miR-181c-5p dramatically promoted pancreatic cancer cell chemoresistance through inactivating the Hippo signaling. GAS5 regulated chemoresistance and Hippo pathway of pancreatic cancer cells via miR-181c-5p/Hippo. Finally, we confirmed that overexpression of GAS5 inhibited tumor growth in pancreatic cancer-bearing mice model. CONCLUSION: GAS5 regualtes Hippo signaling pathway via miR-181c-5p to antagonize the development of multidrug resistance in pancreatic cancer cells.
OBJECTIVE: To explore the core mechanism of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the regulation of multidrug resistance of pancreatic cancer cells. METHODS: mRNA levels of GAS5, miR-181c-5p and Hippo pathway related genes were detected by quantitative real-time PCR (qRT-PCR). Protein levels of MDR-1, MST1, YAP and TAZ were measured by western blot. Cell viability was detected by MTT assay. The combination between GAS5 and miR-181c-5p was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assay. We also established pancreatic cancer-bearing mice model and analyzed tumor volumes. RESULTS: Our data showed GAS5 expression was significantly down-regulated, miR-181c-5p expression was significantly up-regulated in pancreatic cancer cells. Besides, Overexpresson of GAS5 obviously inhibited cell viability, while GAS5 knockdown showed the opposite outcome. Additionally, we also found that GAS5 negatively regulated miR-181c-5p, and miR-181c-5p dramatically promoted pancreatic cancer cell chemoresistance through inactivating the Hippo signaling. GAS5 regulated chemoresistance and Hippo pathway of pancreatic cancer cells via miR-181c-5p/Hippo. Finally, we confirmed that overexpression of GAS5 inhibited tumor growth in pancreatic cancer-bearing mice model. CONCLUSION:GAS5 regualtes Hippo signaling pathway via miR-181c-5p to antagonize the development of multidrug resistance in pancreatic cancer cells.
Authors: Ammad Ahmad Farooqi; Sawera Nayyab; Chiara Martinelli; Rossana Berardi; Hector Katifelis; Maria Gazouli; William C Cho Journal: Front Oncol Date: 2021-06-09 Impact factor: 6.244