Abstract:Objective: To investigate the influence of circular RNA BIRC6 (CircBIRC6) on cisplatin (DDP) resistance of non-small cell lung cancer (NSCLC) cells (A549).Methods: RT-qPCR was used to detect the expression of CircBIRC6 in DDP-resistant and sensitive lung cancer tissues and cells. Human NSCLC cell line A549 and DDP-resistant cells A549/DDP were cultured in vitro. A549/DDP cells were grouped into Control group, pcDNA group, pcBIRC6 group, si-CircBIRC6 group, si-NC group, si-BIRC6+inhibitor NC group, and si-BIRC6+miR-126-5p inhibitor group. RT-qPCR was applied to detect the expression of CircBIRC6 and miR-126-5p; CCK-8 assay was applied to detect cell proliferation and IC50 value for DDP; flow cytometry was applied to detect apoptosis; Western blot was applied to detect the protein expressions of JARID2, Cyclin D1, P21, and P-gp; dual-luciferase reporter gene assay was applied to verify the targeting relationship between CircBIRC6, JARID2 and miR-126-5p. Results: Compared with DDP-sensitive lung cancer tissues, the expression level of CircBIRC6 in DDP-resistant lung cancer tissues was greatly higher; compared with A549 cells, the expression level of CircBIRC6 in A549/DDP cells and the IC50 value of DDP on A549/DDP cells were greatly higher (P<0.05); the dual-luciferase reporter gene assay confirmed that CircBIRC6 and JARID2 had a targeting relationship with miR-126-5p. Compared with the pcDNA group, the A549/DDP cell proliferation, the protein expressions of CircBIRC6, JARID2, Cyclin D1 and P-gp, and IC50 value in the pcBIRC6 group were greatly higher, the apoptosis rate and the expression levels of miR-126-5p and P21 proteins were greatly lower (P<0.05); compared with the si-NC group, the A549/DDP cell proliferation, the protein expressions of CircBIRC6, JARID2, Cyclin D1 and P-gp, and IC50 value in the si-BIRC6 group were greatly lower, the apoptosis rate and the expression levels of miR-126-5p and P21 proteins were greatly higher (P<0.05); down-regulation of miR-126-5p expression reversed the proliferation-inhibiting and apoptosis-promoting effects of inhibiting CircBIRC6 expression on A549/DDP cells. Conclusion: CircBIRC6 is highly expressed in A549/DDP cells, which can inhibit the expression of miR-126-5p by targeting, up-regulate the expression of JARID2, and promote the resistance of A549/DDP cells to DDP.
[1] Kryczka J,Kryczka J,Czarnecka-Chrebelska KH,et al.Molecular mechanisms of chemoresistance induced by cisplatin in NSCLC cancer therapy[J].Int Mol Sci,2021,22(16):8885-8905. [2] Yang H,Zhao M,Zhao L,et al.CircRNA BIRC6 promotes non-small cell lung cancer cell progression by sponging microRNA-145[J].Cell Oncol (Dordr),2020,43(3):477-488. [3] Liu C,Hou J,Shan F,et al.Long non-coding RNA CRNDE promotes colorectal carcinoma cell progression and paclitaxel resistance by regulating miR-126-5p/ATAD2 axis[J].Onco Targets Ther,2020,13(1):4931-4942. [4] Liu B,Wang R,Liu H.mir-126-5p Promotes cisplatin sensitivity of non-small-cell lung cancer by inhibiting ADAM9[J].Biomed Res Int,2021,15(1):1-11. [5] Liu Y,Zhai R,Hu S,et al.Circular RNA circ-RNF121 contributes to cisplatin (DDP) resistance of non-small-cell lung cancer cells by regulating the miR-646/SOX4 axis[J].Anticancer Drugs,2022,33(1):e186-e197. [6] Zhou L,Wang B,Zhang Y,et al.Silencing circBIRC6 inhibits the proliferation,invasion,migration and epithelialmesenchymal transition of bladder cancer cells by targeting the miR4953p/XBP1 signaling axis[J].Mol Med Rep,2021,24(5):811-822. [7] Ni D,Teng J,Cheng Y,et al.circBIRC6 contributes to the development of non-small cell lung cancer via regulating microRNA-217/amyloid beta precursor protein binding protein 2 axis[J].Chin Med (Engl),2022,135(6):714-723. [8] 张靖,白惠娟.circBIRC6靶向miR-367-3p对卵巢癌细胞顺铂耐药性的影响[J].中华肿瘤杂志,2021,43(10):1062-1068. [9] Chen H,Li F,Xue Q.Circ-CUL2/microRNA-888-5p/RB1CC1 axis participates in cisplatin resistance in NSCLC via repressing cell advancement[J].Bioengineered,2022,13(2):2828-2840. [10] Lima Queiroz A,Zhang B,Comstock DE,et al.miR-126-5p targets malate dehydrogenase 1 in non-small cell lung carcinomas[J].Biochem Biophys Res Commun,2018,499(2):314-320. [11] Han F,Huang D,Meng J,et al.miR-126-5p enhances radiosensitivity of lung adenocarcinoma cells by inhibiting EZH2 via the KLF2/BIRC axis[J].Cell Mol Med,2022,26(9):2529-2542. [12] Wang X,Lyu J,Ji A,et al.Jarid2 enhances the progression of bladder cancer through regulating PTEN/AKT signaling[J].Life Sci,2019,230(1):162-168. [13] Kuang W,Jiang W,Chen Y,et al.The function and mechanism of the JARID2/CCND1 axis in modulating glioma cell growth and sensitivity to temozolomide (TMZ)[J].Cancer Biol Ther,2021,22(5-6):392-403. [14] Wang Q,Wu J,Wei H,et al.JARID2 promotes stemness and cisplatin resistance in non-small cell lung cancer via upregulation of Notch1[J].Int Biochem Cell Biol,2021,138(1):1-9.