Department of Breast Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province 430079, China.
Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province 430079, China.
Aging (Albany NY). 2021 Aug 10;13(15):19306-19316. doi: 10.18632/aging.203272.
Triple negative breast cancer (TNBC) is a group of highly heterogeneous mixed breast cancer at the level of gene expression profile. Therefore, it is of great clinical significance to explore the molecular mechanism of TNBC and find a targeted therapeutic approach from the molecular level.
Long non-coding RNA (lncRNA) HAGLR expression level was measured by and qRT-PCR in TNBC tissues and cell lines. EdU, MTT, wound healing and Transwell assays were performed to explore the role of HAGLR on the malignancy of TNBC cells. Luciferase assay was used to clarify the binding between miR-335-3p with HAGLR and WNT2. The tumor formation experiment in nude mice was used to explore the function of HAGLR .
HAGLR was increased in TNBC tissues and cell lines. Silencing of HAGLR inhibited viability, proliferation, migration, and invasion of BT549 cells. Furthermore, HAGLR acted as a sponge of miR-335-3p and inhibited its expression. And miR-335-3p directly targeted WNT2. Functionally, forced expression of miR-335-3p or knockdown of WNT2 removed the promoted effects of lncRNA HAGLR on TNBC development. tumorigenesis experiments indicated HAGLR accelerated tumor growth via miR-335-3p/WNT2 axis.
Our study revealed that HAGLR promoted the growth of TNBC, which was mediated by miR-335-3p/WNT2 axis.
三阴性乳腺癌（TNBC）是一组在基因表达谱水平上高度异质的混合乳腺癌。因此，从分子水平上探讨 TNBC 的分子机制，寻找靶向治疗方法具有重要的临床意义。
采用 qRT-PCR 检测 TNBC 组织和细胞系中长链非编码 RNA（lncRNA）HAGLR 的表达水平。EdU、MTT、划痕愈合和 Transwell 实验用于探讨 HAGLR 对 TNBC 细胞恶性行为的作用。荧光素酶报告实验用于阐明 miR-335-3p 与 HAGLR 和 WNT2 之间的结合。裸鼠肿瘤形成实验用于探讨 HAGLR 的功能。
HAGLR 在 TNBC 组织和细胞系中表达增加。沉默 HAGLR 抑制 BT549 细胞的活力、增殖、迁移和侵袭。此外，HAGLR 作为 miR-335-3p 的海绵，抑制其表达。miR-335-3p 直接靶向 WNT2。功能上，miR-335-3p 的过表达或 WNT2 的敲低消除了 lncRNA HAGLR 对 TNBC 发展的促进作用。肿瘤发生实验表明，HAGLR 通过 miR-335-3p/WNT2 轴加速肿瘤生长。
我们的研究表明，HAGLR 通过 miR-335-3p/WNT2 轴促进了 TNBC 的生长。
