Diao Biyu, Cai Yangjun, Song Dandan, Hu Yingying, Xie Bojian, Kan Yang, Hu Xiaoqu
Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, No. 96, Fuxue Lane, Lucheng District, Wenzhou, 325000, China.
Department of Thyroid and Breast Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, 318000, China.
Breast Cancer Res Treat. 2025 Jun;211(3):727-741. doi: 10.1007/s10549-025-07695-6. Epub 2025 Apr 9.
Breast cancer (BC) has become the most common malignant tumor in women worldwide. This study was carried out to find and validate a novel molecular therapeutic target for BC.
Long non-coding RNA (lncRNA) AK023507 was selected as the study objects through microarray analysis. The function of lncRNA AK023507 was verified by various cell function experiments in vitro, subcutaneous tumorigenesis experiments, and lung metastasis model experiments in vivo. The RNA pull-down experiment and Western blot experiment were used to confirm the mechanism regulation pathway and the recovery experiment was used to verify it. TCGA datasets were used for clinical and immune function prediction analysis.
In vitro cell function tests and in vivo experiments suggested that overexpression of lncRNA AK023507 inhibited the proliferation and metastasis of BC cells. The RNA pull-down experiment and Western blot analysis validated that lncRNA AK023507 interacted with the dedicator of cytokinesis 4 (DOCK4) protein. Analysis of public databases predicted that DOCK4 is a potential prognostic risk factor associated with epithelial-mesenchymal transition (EMT) and central memory T cell (TCM) cellular immune infiltration.
LncRNA AK023507 inhibits the proliferation and metastasis of BC by regulating the DOCK4/β-catenin axis. This discovery will provide new potential therapeutic targets for BC.
乳腺癌已成为全球女性中最常见的恶性肿瘤。本研究旨在寻找并验证一种新的乳腺癌分子治疗靶点。
通过微阵列分析选择长链非编码RNA(lncRNA)AK023507作为研究对象。lncRNA AK023507的功能通过体外各种细胞功能实验、皮下成瘤实验和体内肺转移模型实验进行验证。采用RNA下拉实验和蛋白质印迹实验确认机制调控途径,并通过回复实验进行验证。利用癌症基因组图谱(TCGA)数据集进行临床和免疫功能预测分析。
体外细胞功能测试和体内实验表明,lncRNA AK023507的过表达抑制了乳腺癌细胞的增殖和转移。RNA下拉实验和蛋白质印迹分析证实lncRNA AK023507与胞质分裂调控蛋白4(DOCK4)相互作用。公共数据库分析预测,DOCK4是与上皮-间质转化(EMT)和中央记忆T细胞(TCM)细胞免疫浸润相关的潜在预后风险因素。
lncRNA AK023507通过调节DOCK4/β-连环蛋白轴抑制乳腺癌的增殖和转移。这一发现将为乳腺癌提供新的潜在治疗靶点。