Department of General Surgery, Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Xi-Cheng District, Beijing 100050, China.
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, Zhejiang 325000, China.
J Biochem. 2021 Jul 3;169(5):601-611. doi: 10.1093/jb/mvaa148.
In recent years, the role of circular RNAs (circRNAs) in tumours has attracted widespread attention. Some circRNAs have been reported to play a role in triple-negative breast cancer (TNBC). However, circRNAs have rarely been reported in terms of TNBC resistance. This study aimed to clarify that circGFRA1 affects the sensitivity of TNBC cells to paclitaxel (PTX) by the miR-361-5p/TLR4 pathway. Compared with the non-PTX-resistant TNBC cell line MDA-MB-231, the expression of circGFRA1 in the PTX-resistant TNBC cell line MDA-MB-231.PR was significantly increased. The small hairpin RNA-mediated circGFRA1 knockdown inhibited the resistance of TNBC cells to PTX. RNA pull-down assay and luciferase reporter gene assay confirmed the binding between circGFRA1 and miR-361-5p and between miR-361-5p and TLR4. It has been proven that circGFRA1 knockdown can inhibit the resistance of TNBC cells to PTX by promoting the expression of miR-361-5p, and subsequently reduce the expression of TLR4.
近年来，环状 RNA（circRNAs）在肿瘤中的作用引起了广泛关注。一些 circRNAs 已被报道在三阴性乳腺癌（TNBC）中发挥作用。然而，关于 circRNAs 在 TNBC 耐药方面的报道很少。本研究旨在通过 miR-361-5p/TLR4 通路阐明 circGFRA1 通过影响 TNBC 细胞对紫杉醇（PTX）的敏感性来发挥作用。与非 PTX 耐药的 TNBC 细胞系 MDA-MB-231 相比，PTX 耐药的 TNBC 细胞系 MDA-MB-231.PR 中 circGFRA1 的表达显著增加。circGFRA1 的小发夹 RNA 介导的敲低抑制了 TNBC 细胞对 PTX 的耐药性。RNA 下拉实验和荧光素酶报告基因实验证实了 circGFRA1 与 miR-361-5p 之间以及 miR-361-5p 与 TLR4 之间的结合。已经证明，circGFRA1 的敲低通过促进 miR-361-5p 的表达来抑制 TNBC 细胞对 PTX 的耐药性，进而降低 TLR4 的表达。
