Shi Yue, Han Tao, Liu Chong
Department of Geriatric Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Ann Transl Med. 2021 Aug;9(15):1236. doi: 10.21037/atm-21-2934.
Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer (BC) subtypes. Circular ribonucleic acids (circRNAs) are a class of novel stable and conserved forms of ribonucleic acids (RNAs). circRNAs have been documented to be involved in multiple diseases, especially malignancies, through a competing endogenous RNA (ceRNA) mechanism. However, few studies have been conducted on the function of circRNAs in TNBC. Previously, hsa_circ_0006220 was found to be downregulated in BC tissues. The present study sought to explore the mechanism of hsa_circ_0006220 in TNBC progression.
A real-time polymerase chain reaction (PCR) was used to validate the expression of hsa_circ_0006220 in TNBC tissues and cells. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), wound-healing and Transwell assays were conducted to measure the inhibition effects of hsa_circ_0006220 on TNBC cells . Further, a dual-luciferase reporter assay was performed to confirm the interaction between hsa_circ_0006220 and miR-197-5p. A mimic and an inhibitor of miR-197-5p were constructed to confirm the downstream mechanism of hsa_circ_0006220 in TNBC cells.
Hsa_circ_0006220 was more downregulated in TNBC than other subtypes of BC tissues and cell lines. data showed that hsa_circ_0006220 remarkably inhibited the proliferation, migration, and invasion of TNBC cells. Further, hsa_circ_0006220 was confirmed to be a sponge of miR-197-5p, and to indirectly regulate CDH19 expression. A rescue assay indicated the biological function of the hsa_circ_0006220/miR-197-5p/CDH19 pathway in TNBC cells.
hsa_circ_0006220 plays an inhibitory role in TNBC progression. It might be a potential diagnostic marker and therapeutic target for TNBC patients.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌（BC）亚型之一。环状核糖核酸（circRNAs）是一类新型的稳定且保守的核糖核酸（RNAs）形式。已有文献记载，circRNAs通过竞争性内源RNA（ceRNA）机制参与多种疾病，尤其是恶性肿瘤。然而，关于circRNAs在TNBC中的功能研究较少。此前，已发现hsa_circ_0006220在BC组织中表达下调。本研究旨在探索hsa_circ_0006220在TNBC进展中的机制。
采用实时聚合酶链反应（PCR）验证hsa_circ_0006220在TNBC组织和细胞中的表达。此外，进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四氮唑溴盐（MTT）、伤口愈合和Transwell实验，以检测hsa_circ_0006220对TNBC细胞的抑制作用。进一步，进行双荧光素酶报告基因实验，以证实hsa_circ_0006220与miR-197-5p之间的相互作用。构建miR-197-5p的模拟物和抑制剂，以证实hsa_circ_0006220在TNBC细胞中的下游机制。
与其他BC组织和细胞系亚型相比，hsa_circ_0006220在TNBC中表达下调更明显。数据显示，hsa_circ_0006220显著抑制TNBC细胞的增殖、迁移和侵袭。此外，已证实hsa_circ_0006220是miR-197-5p的海绵，并间接调节CDH19的表达。一项挽救实验表明了hsa_circ_0006220/miR-197-5p/CDH19通路在TNBC细胞中的生物学功能。
hsa_circ_0006220在TNBC进展中起抑制作用。它可能是TNBC患者潜在的诊断标志物和治疗靶点。
