The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
The Second Department of Urology Surgery, Tangshan People's Hospital; 4Department of Breast Health Care, Maternal and Child Care Service Centre, Tangshan, Hebei 063000, P.R. China.
Mol Med Rep. 2022 Feb;25(2). doi: 10.3892/mmr.2021.12567. Epub 2021 Dec 16.
CircRNAs are associated with adriamycin (ADM) resistance in triple‑negative breast cancer (TNBC), but the mechanism is unknown. Reverse transcription‑quantitative PCR was applied to quantify circular RNA (circRNA)_0044556, microRNA (miR)‑145 and NRAS proto‑oncogene, GTPase (NRAS) in TNBC tissues and cells with or without ADM treatment. Following ADM treatment, the effects of circRNA_0044556 on the viability, ADM resistance, apoptosis and migration of TNBC cells were investigated by cell function experiments (Cell Counting Kit‑8, flow cytometry and Transwell assays). The targeting relationship between circRNA_0044556 and miR‑145 was investigated via bioinformatics analysis, dual‑luciferase reporter assay and RNA immunoprecipitation. The effects of the circRNA_0044556/miR‑145 axis on the TNBC cells were revealed by rescue experiments. Correlations among circRNA_0044556, miR‑145 and NRAS were analyzed by Pearson's correlation test. CircRNA_0044556 was highly expressed in TNBC tissues and cells with or without ADM‑resistance. The overexpression of circRNA_0044556 promoted cell viability, ADM‑resistance and migration, while inhibiting the apoptosis by sponging miR‑145. Upregulation of miR‑145 reversed the effects of circRNA_0044556 on the TNBC cells. CircRNA_0044556 was negatively correlated with miR‑145 yet positively correlated with NRAS, the target gene of miR‑145, in addition to the discovery suggesting the negative regulatory effects of circRNA_0044556 on miR‑145. CircRNA_0044556 diminished the sensitivity of TNBC cells to ADM via the miR‑145/NRAS axis.
环状 RNA（circRNA）与三阴性乳腺癌（TNBC）的阿霉素（ADM）耐药相关，但具体机制尚不清楚。采用逆转录定量 PCR 检测 TNBC 组织及经 ADM 处理或未处理的细胞中环状 RNA（circRNA）_0044556、微小 RNA（miR）-145 和 NRAS 原癌基因，GTP 酶（NRAS）的表达。通过细胞功能实验（细胞计数试剂盒-8、流式细胞术和 Transwell 分析）研究 circRNA_0044556 对 TNBC 细胞活力、ADM 耐药性、细胞凋亡和迁移的影响。通过生物信息学分析、双荧光素酶报告基因检测和 RNA 免疫沉淀实验研究 circRNA_0044556 与 miR-145 的靶向关系。通过挽救实验揭示 circRNA_0044556/miR-145 轴对 TNBC 细胞的影响。采用 Pearson 相关检验分析 circRNA_0044556、miR-145 与 NRAS 之间的相关性。circRNA_0044556 在 ADM 耐药或不耐药的 TNBC 组织和细胞中高表达。circRNA_0044556 的过表达促进细胞活力、ADM 耐药性和迁移，同时通过海绵吸附 miR-145 抑制细胞凋亡。miR-145 的上调逆转了 circRNA_0044556 对 TNBC 细胞的影响。circRNA_0044556 与 miR-145 呈负相关，与 miR-145 的靶基因 NRAS 呈正相关，此外还发现 circRNA_0044556 对 miR-145 具有负调控作用。circRNA_0044556 通过 miR-145/NRAS 轴降低 TNBC 细胞对 ADM 的敏感性。
