Identification of circ_0058357 as a regulator in non‐small cell lung cancer cells resistant to cisplatin by miR‐361‐3p/ABCC1 axis
| Autor: | Jiang Shi, Dan Chu, Pengpeng Li, Peng-Fei Jiao, Ya-Meng Li, Siyuan Huang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Lung Neoplasms endocrine system diseases Cell Survival ABCC1 Antineoplastic Agents Apoptosis NSCLC Flow cytometry Mice Carcinoma Non-Small-Cell Lung circ_0058357 Medicine Cytotoxic T cell Animals Humans MTT assay RC254-282 Cell Proliferation Cisplatin Reporter gene Mice Inbred BALB C medicine.diagnostic_test business.industry Cell growth chemoresistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens General Medicine Original Articles RNA Circular Xenograft Model Antitumor Assays In vitro miR‐361‐3p MicroRNAs Oncology A549 Cells Drug Resistance Neoplasm Cancer research Original Article Female Multidrug Resistance-Associated Proteins business medicine.drug |
| Zdroj: | Thoracic Cancer, Vol 12, Iss 21, Pp 2894-2906 (2021) Thoracic Cancer |
| ISSN: | 1759-7706 1759-7714 |
| Popis: | Background Drug resistance is a major clinical drawback behind the failure of chemotherapy in non‐small cell lung cancer (NSCLC). In this study, we undertook to identify the precise role of circular RNA (circRNA) circ_0058357 in the functional properties of DDP‐resistant NSCLC cells. Methods Circ_0058357, miR‐361‐3p and ATP‐binding cassette (ABC) subfamily C member 1 (ABCC1) were quantified by qRT‐PCR and western blot. Cell survival and viability were gauged by MTT assay. Cell proliferation, apoptosis, invasion and migration were measured by EdU, flow cytometry, transwell and wound‐healing assays, respectively. The direct relationship between miR‐361‐3p and circ_0058357 or ABCC1 was validated by dual‐luciferase reporter assay. Results Our data showed that circ_0058357 was highly expressed in DDP‐resistant NSCLC tissues and cells. Inhibition of circ_0058357 repressed cell growth, invasion, migration, and promoted DDP sensitivity and cell apoptosis of H1299/DDP and A549/DDP cells in vitro. Moreover, inhibition of circ_0058357 diminished the growth of A549/DDP cells and sensitized them to the cytotoxic effect of DDP in vivo. Mechanistically, circ_0058357 contained a miR‐361‐3p binding site and miR‐361‐3p was identified as a molecular mediator of circ_0058357 regulation. MiR‐361‐3p suppressed ABCC1 expression by binding to ABCC1 3′UTR, and miR‐361‐3p‐mediated inhibition of ABCC1 affected the growth, invasion, migration, apoptosis and DDP sensitivity of H1299/DDP and A549/DDP cells. Furthermore, circ_0058357 regulated ABCC1 expression by competitively binding to shared miR‐361‐3p. Conclusions Our findings identified that inhibition of circ_0058357 suppresses the growth and metastasis of H1299/DDP and A549/DDP cells and sensitizes them to DDP therapy partially by targeting the miR‐361‐3p/ABCC1 axis. Circ_0058357 affects ABCC1 expression through miR‐361‐3p. H1299/DDP (a) and A549/DDP (b) cells were transfected with si‐circ_0058357 + anti‐miR‐361‐3p, si‐circ_0058357 + anti‐miR‐NC, si‐circ_0058357 or si‐NC and checked for ABCC1 protein level by western blot. |
| Databáze: | OpenAIRE |
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