环状 RNA hsa_circ_0043278 通过 miR-455-3p/EI24 信号通路抑制乳腺癌进展。
Circular RNA hsa_circ_0043278 inhibits breast cancer progression via the miR-455-3p/EI24 signalling pathway.
机构信息
Department of Geriatric Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
出版信息
BMC Cancer. 2021 Nov 20;21(1):1249. doi: 10.1186/s12885-021-08989-w.
BACKGROUND
Breast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.
METHODS
The levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.
RESULTS
Hsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.
CONCLUSION
Hsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.
背景
乳腺癌（BC）是全球主要的恶性肿瘤之一。环状核糖核酸（circRNAs）是一类保守的核糖核酸（RNA）分子，在各种疾病中发挥重要作用。最近，circRNAs 被认为具有诊断价值，可能作为 BC 的潜在诊断生物标志物。先前发现 hsa_circ_0043278 在人 BC 中下调。然而，其在人 BC 中的作用尚未确定。
方法
通过实时定量逆转录聚合酶链反应（qRT-PCR）验证 BC 细胞系中 hsa_circ_0043278 的水平。hsa_circ_0043278 的过表达载体和短发夹 RNA（shRNA）分别转染至 MDA-MB-231 和 MCF-7 细胞中。通过 3-(4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴盐（MTT）、集落形成、划痕愈合和 Transwell 分析，在体外测量 hsa_circ_0043278 对肿瘤细胞生长、迁移和侵袭的影响。进行异种移植实验以验证 hsa_circ_0043278 对肿瘤生长的抑制作用。通过双荧光素酶报告基因实验证实 hsa_circ_0043278 与 miR-455-3p 之间的相互作用。设计 miR-455-3p 的模拟物和抑制剂以确认 hsa_circ_0043278 对 hsa_circ_0043278/miR-455-3p/依托泊苷诱导基因 24（EI24）轴的影响。
结果
hsa_circ_0043278 在 BC 细胞系中下调。此外，hsa_circ_0043278 的过表达显著降低了 BC 细胞活力，并抑制了 BC 细胞在体外的迁移和侵袭，并抑制了体内肿瘤生长。hsa_circ_0043278 的下调导致了相反的结果。hsa_circ_0043278 的表达与 miR-455-3p 的表达呈负相关。此外，机制研究证明 hsa_circ_0043278 可直接与 miR-455-3p 结合，并调节 BC 细胞中 EI24 和 NF-κB 的表达。
结论
hsa_circ_0043278 通过 hsa_circ_0043278/miR-455-3p/EI24 轴在 BC 中作为肿瘤抑制基因发挥作用，可能被视为 BC 的新预后预测因子或潜在治疗靶点。
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