Cancer Management and Research (May 2020)
Targeted Inhibition of CCL22 by miR-130a-5p Can Enhance the Sensitivity of Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy
Abstract
Qing-Liang Fang,1,* Kai-Chun Li,2,* Lei Wang,1 Xiang-Lian Gu,1 Ren-Jie Song,1 Song Lu1 1Department of Radiation Oncology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Oncology, Tianyou Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-Liang FangDepartment of Radiation Oncology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel +8621-64385700Email [email protected]: This study set out to explore the regulatory mechanism of miR-130a-5p in cisplatin (DDP)-resistant gastric cancer (GC) cells.Materials and Methods: Forty cases of GC and paracancerous tissues were collected, and the miR-130a-5p and CCL22 levels were detected by qRT-PCR. DDP-resistant cell lines of GC cells were established. Cell viability, invasion, and apoptosis were measured by CCK-8, Transwell, and flow cytometry, respectively. The relationship between miR-130a-5p and CCL22 was verified by dual-luciferase reporter enzyme, and the protein levels of caspase-3, bax, bcl-2, and CCL22 were determined by Western blot.Results: miR-130a-5p was low expressed in GC tissues and cells, while CCL22 showed marked negative correlation, and the area under the curve (AUC) for diagnosing GC was not less than 0.850. Up-regulating miR-130a-5p or knocking down CCL22 expression can inhibit the proliferation and invasion of GC cells and promote their apoptosis, reverse the resistance of NCI-N87/DDP to DDP, and also enhance the chemosensitivity of GC cells. Dual-luciferase reporter enzyme identified that there was a targeted relationship between miR-130a-5p and CCL22. At the same time, miR-130a-5p and CCL22 were up-regulated or down-regulated, and the malignant proliferation, invasion, apoptosis, and DDP chemotherapy resistance of the cells had no difference compared with miR-NC with transfection-unrelated sequences.Conclusion: Up-regulating miR-130a-5p can enhance the sensitivity of DDP-resistant GC cells to chemotherapy and regulate their biological function by targeted inhibition of CCL22.Keywords: miR-130a-5p, CCL22, cisplatin, gastric cancer, chemosensitivity
