miR-4486 enhances cisplatin sensitivity of gastric cancer cells by restraining the JAK3/STAT3 signalling pathway
| Autor: | Zhe Huang, Caijin Zhou, Rihong Chen, Linxia Chen, Weiwei Wang, Feipeng Xu, Qingwen Xu, Renwei Huang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine endocrine system diseases Cell Survival 030106 microbiology Antineoplastic Agents Apoptosis Flow cytometry Inhibitory Concentration 50 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Cell Line Tumor medicine Humans Pharmacology (medical) Viability assay STAT3 Pharmacology Cisplatin Dose-Response Relationship Drug biology medicine.diagnostic_test Chemistry Janus Kinase 3 Hedgehog signaling pathway MicroRNAs Infectious Diseases Oncology Cell culture 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research Signal Transduction medicine.drug |
| Zdroj: | Journal of Chemotherapy. 34:35-44 |
| ISSN: | 1973-9478 1120-009X |
| DOI: | 10.1080/1120009x.2021.1936957 |
| Popis: | Along with the occurrence of cisplatin resistance, treatment on gastric cancer (GC) becomes difficult. Therefore, researches on new therapeutic methods to revert cisplatin resistance are becoming increasingly urgent. qRT-PCR was used to quantify the expression of miR-4486, JAK3 in SGC-7901 or SGC-7901/DDP cell lines. WB was utilized to analyze the expression of JAK3, STAT3 and p-STAT3 in SGC-7901/DDP cell lines. CCK-8 assay was used to determine the IC50 of cisplatin on both cell lines and cell viability of SGC-7901/DDP cell lines. The target relationship between miR-4486 and JAK3 was determined by luciferase assay. MiR-4486 expression on apoptosis of SGC-7901/DDP cell lines was determined by flow cytometry. qRT-PCR testified that miR-4486 decreased in SGC-7901/DDP cells, and the expression of miR-4486 mimic increased significantly compared with miR-4486 NC. By CCK-8 assay, the IC50 of cisplatin on both cell lines were 9 μg/mL and 81.3 μg/mL, and overexpression of miR-4486 decreased the viability of SGC-7901/DDP cells. Compared with DDP group, the expression of miR-4486 accelerated SGC-7901/DDP cells apoptosis. Dual-luciferase assay suggested that JAK3 was the target gene of miR-4486. qRT-PCR and WB proved that miR-4486/JAK3 axis inhibit the activation of JAK3/STAT3 pathway, and JAK3 overexpression can partly reverse this. As shown by CCK-8 and flow cytometry, miR-4486 overexpression decreased viability and stimulated apoptosis of SGC-7901/DDP cells. However, JAK3 overexpression can also partly revert this. miR-4486 overexpression could decrease viability and improve apoptosis of SGC-7901/DDP cells to revert its cisplatin-resistance, and the mechanism may be related to JAK3/STAT3 signalling pathway. |
| Databáze: | OpenAIRE |
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