MiR-149-3p promotes the cisplatin resistance and EMT in ovarian cancer through downregulating TIMP2 and CDKN1A

• DOI: 10.1186/s13048-021-00919-5
• Publication Date: 2021-11-19T16:03:41Z
• Authors: Jin Wang; Lingxia Liu
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; TIMP2; Epithelial-Mesenchymal Transition; Mice; 03 medical and health sciences; Ovarian cancer; Cell Line, Tumor; Animals; Humans; Cisplatin resistance; Ovarian Neoplasms; Tissue Inhibitor of Metalloproteinase-2; Research; Gynecology and obstetrics; miR-149-3p; Prognosis; Xenograft Model Antitumor Assays; 3. Good health; CDKN1A; Gene Expression Regulation, Neoplastic; MicroRNAs; Drug Resistance, Neoplasm; RG1-991; Female; Cisplatin

Abstract Background Ovarian cancer (OC), a kind of gynecological cancer, is characterized by high mortality rate, with microRNAs (miRNAs) playing essential roles in it. However, the clinical significance miRNAs and their molecular mechanisms OC are mostly unknown. Methods miR-149-3p expression was predicted through Gene Expression Omnibus (GEO) data confirmed q-PCR various cells tissues from patients different characteristics. Moreover, its terms proliferation, migration invasion were measured CCK-8, colony formation, wound healing transwell assays including cisplatin-resistant cisplatin-sensitive cells. And effect on epithelial-mesenchymal transition also assessed detecting related protein expression. Additionally, potential targets verified dual luciferase assay Ago-RIP assay. Finally, oncogenic functions explored vivo. Results In GSE79943, GSE131790, TCGA, found to be highly expressed associated poor survival. metastasis chemoresistant cells, confirmed. tumorigenic effects, knockdown inhibited cisplatin resistance other malignant phenotypes, while overexpression led contrary results. Mechanistically, targeted 3’UTR CDKN1A TIMP2 function as an miRNA. Conclusion brief , promoted EMT downregulating TIMP2, which might provide therapeutic target for treatment.