Identification of circ_0058357 as a regulator in non‐small cell lung cancer cells resistant to cisplatin by miR‐361‐3p/ABCC1 axis

Abstract

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.

Circular RNA circ_0002360 regulates the Taxol resistance and malignant behaviors of Taxol-resistant non-small cell lung cancer cells by microRNA-585-3p-dependent modulation of G protein regulated inducer of neurite outgrowth 1

“…The EdU experiment was operated according to the instructions of the EdU Apollo488/567 in vitro kit (Solarbio) as reported [ 27 ]. Briefly, transfected H1299/Taxol and A549/Taxol cells (4,000 cells/well) were seeded in 96-well dishes for 48 h, treated with 50 nM of EdU reagent for 2 h, and then dyed with 1× Apollo488/567 for 30 min, followed by the nucleus staining with 4’,6-diamidino-2-phenylindole (DAPI, Solarbio) for 30 min.…”

“…After transfection, ~1,000,000 H1299/Taxol and A549/Taxol cells were harvested and stained in accordance with the Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis detection kit (Solarbio) specifications as described elsewhere [ 27 ]. A total of 100,000 events were analyzed by Cytoflex flow cytometry (BECKMAN COULTER, Pasadena, Texas, USA), and the apoptotic cells were defined as the cells that was positive with Annexin V.…”

“…Animal experimental procedures were done according to the methods reported by Chu et al . [ 27 ]. 1 × 10 6 A549/Taxol cells infected with a lentiviral sh-NC or sh-circ_0002360 construct were injected into the axilla of BALB/c nude mice (female, 5–7 weeks old, Beijing Vital River Laboratory Animal Technology Co., Ltd., Beijing, China).…”

Circular RNAs in chemotherapy resistance of lung cancer and their potential therapeutic application

“…Moreover, circ‐PIP5K1A could sponge miR‐101, promoted the increased expression of ABCC1, and then regulated the progression and cisplatin sensitivity of NSCLC 51 . Furthermore, the expression of ABCC1 and cisplatin sensitivity were also regulated by circ‐PVT1 in lung adenocarcinoma 52 and by circ_0058357 in NSCLC 53 . In addition, Liang et al reported that circRNA_103615 promoted ABCB1 expression and the cisplatin resistance of NSCLC 54 .…”

MiRNA-Based Therapies for Lung Cancer: Opportunities and Challenges?

“…For instance, hsa-miR-98-5p inhibits the expression of copper transporter 1 (CTR1) to reverse CP resistance in NSCLC [ 55 ]. By targeting the miR-361-3p/ABCC1 axis, circ0058357 inhibition reduces the proliferation and metastasis of NSCLC cells and partially sensitizes them to CP [ 56 ]. In addition, miR-1914-3p can also reverse chemoresistance by regulating yes-associated protein (YAP) [ 57 ].…”