Affiliation: | 1. Department of Clinical Oncology, Fourth Military Medical University, Xi'an, Shaanxi, China ITC &WM Dept of Shaanxi Province Oncology Hospital, Xi'an, Shaanxi, China;2. ITC &WM Dept of Shaanxi Province Oncology Hospital, Xi'an, Shaanxi, China;3. Department of Drug and Equipment, Number 534 Hospital, PLA, Luoyang, Henan, China Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, China;4. Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, China Department of Reproductive Medical Center, No.181 Hospital of Chinese People's Liberation Army, Guilin, Guanxi, China;5. Department of Clinical Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China;6. Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, China |
Abstract: | To determine the correlation between QKI and pancreatic cancer tissues, the QKI expression of pancreatic cancer cells and fibroblasts in the tumor-surrounding microenvironment were detected. Then, QKI overexpression and interference with QKI short hairpin RNA in LX-2 (a fibroblast cell line) were established in vitro. Meanwhile, to observe the cell proliferation, invasion, migration, and other changes, QKI, and related epithelial-mesenchymal transition (EMT) molecules were detected by a polymerase chain reaction and Western blot analysis. In addition, an in vivo tumorigenicity test in node mice was performed to confirm whether QKI expression can promote the proliferation, invasion, and metastasis of pancreatic cancer ductal epithelial cells. Finally, the autophagy levels of fibroblasts with QKI overexpression were observed by electron microscopy to further explore the QKI pathogenic mechanism. It was found that cell proliferation, invasion, migration, and EMT-related markers were increased in QKI-overexpressed fibroblasts LX-2. Furthermore, in vivo, liver and peritoneal metastasis decreased overall survival rate and increasing autophagy levels in QKI-overexpressing nude mice were observed. Meanwhile, knock down QKI with small interfering RNA can reverse all the above effects. QKI can promote the proliferation, metastasis, and invasion of pancreatic cancer through activating fibroblasts surrounding pancreatic cancer and accelerating EMT and increasing the autophagy in pancreatic cancer. QKI may become a potential target for the treatment of pancreatic cancer. |