Li Ling, Qu Wen-Hui, Ma Hui-Ping, Wang Li-Li, Zhang Yan-Bo, Ma Yuan
Department of Oncology, Affiliated Tengzhou Central People's Hospital of Jining Medical University, Jining Medical University, Tengzhou, Shandong Province, China.
Department of Anesthesiology, Affiliated Tengzhou Central People's Hospital of Jining Medical University, Jining Medical University, Tengzhou, Shandong Province, China.
Arch Physiol Biochem. 2022 Jun;128(3):657-665. doi: 10.1080/13813455.2020.1716019. Epub 2020 Jan 29.
This research was designed to detect the function of low-density lipoprotein receptor (LDLR)-related protein 8 (LRP8) in breast cancer (BC). Our results revealed that LRP8 was highly expressed in BC tissues and cell lines compared with human normal breast tissues. The poor prognosis of patients with BC was associated with the up-regulation of LRP8 while inversely connected with overexpression of miR-1262. Functionally, LRP8 depletion in BC cells impaired the proliferative, clonogenic, invasive, and migratory capabilities, which was consistent with the effects of upregulated miR-1262. Bioinformatics prediction and luciferase reporter assay confirmed that miR-1262 was an upstream factor for LRP8 and negatively regulated the expression of LRP8. Further experiments illustrated that the co-transfection of miR-1262 antamir and si-LRP8 could significantly suppress the promoting impacts caused by the transfection of miR-1262 antamir alone. These findings highlighted that LRP8 accelerated the BC development by contributing cellular aggressiveness, which was modulated by miR-1262.
本研究旨在检测低密度脂蛋白受体（LDLR）相关蛋白8（LRP8）在乳腺癌（BC）中的作用。我们的结果显示，与人类正常乳腺组织相比，LRP8在BC组织和细胞系中高表达。BC患者的不良预后与LRP8的上调相关，而与miR-1262的过表达呈负相关。在功能上，BC细胞中LRP8的缺失损害了其增殖、克隆形成、侵袭和迁移能力，这与上调miR-1262的作用一致。生物信息学预测和荧光素酶报告基因检测证实，miR-1262是LRP8的上游因子，并负向调节LRP8的表达。进一步的实验表明，共转染miR-1262拮抗剂和si-LRP8可显著抑制单独转染miR-1262拮抗剂所产生的促进作用。这些发现突出表明，LRP8通过促进细胞侵袭性加速了BC的发展，而这一过程受miR-1262的调控。
