He Lin, Tang Lingfeng, Wang Rui, Liu Li, Zhu Pengpeng, Jiang Kunwei, Tu Gang
Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
Pathol Res Pract. 2022 Jun;234:153891. doi: 10.1016/j.prp.2022.153891. Epub 2022 Apr 9.
This research aims to investigate the effect of lncRNA KB-1980E6.3 on the biological behaviour of breast cancer cells under normoxic conditions and the underlying molecular mechanism. The expression of KB-1980E6.3 in breast cancer tissues and cells was detected by RT-qPCR. The proliferation, migration and invasion of cells were evaluated by CCK-8, colony formation, scratch and Transwell assays; KB-1980E6.3-related xenograft models were established for in vivo studies. The protein expression of PI3K, p-PI3K, AKT and p-AKT was validated by western blotting analysis. The levels of KB-1980E6.3 are significantly upregulated in breast cancer tissues and cells and are related to the poor prognosis. Functional research both in vivo and in vitro revealed that the downregulation of KB-1980E6.3 expression significantly decreased cell proliferation, invasion and migration, while ectopic KB-1980E6.3 expression obviously promoted these biological phenotypes. In terms of the mechanism, KB-1980E6.3 is involved in the activation of the PI3K/AKT signalling pathway. Knockdown of KB-1980E6.3 reduced the expression of the p-PI3K and p-AKT proteins, whereas KB-1980E6.3 overexpression showed the opposite result. The agonist 740Y-P and inhibitor LY294002 reversed the effect of KB-1980E6.3 knockdown and overexpression on the PI3K/AKT pathway in BC cells. KB-1980E6.3 promotes the proliferation, invasion and migration of breast cancer cells by activating PI3K/AKT signalling, which can be used as a potential target for breast cancer therapy.
本研究旨在探讨lncRNA KB-1980E6.3在常氧条件下对乳腺癌细胞生物学行为的影响及其潜在分子机制。采用RT-qPCR检测KB-1980E6.3在乳腺癌组织和细胞中的表达。通过CCK-8、集落形成、划痕和Transwell实验评估细胞的增殖、迁移和侵袭能力；建立与KB-1980E6.3相关的异种移植模型用于体内研究。通过蛋白质印迹分析验证PI3K、p-PI3K、AKT和p-AKT的蛋白表达。KB-1980E6.3在乳腺癌组织和细胞中的水平显著上调，且与预后不良相关。体内和体外功能研究表明，KB-1980E6.3表达下调显著降低细胞增殖、侵袭和迁移，而异位表达KB-1980E6.3则明显促进这些生物学表型。在机制方面，KB-1980E6.3参与PI3K/AKT信号通路的激活。敲低KB-1980E6.3可降低p-PI3K和p-AKT蛋白的表达，而KB-1980E6.3过表达则呈现相反结果。激动剂740Y-P和抑制剂LY294002可逆转KB-1980E6.3敲低和过表达对乳腺癌细胞PI3K/AKT通路的影响。KB-1980E6.3通过激活PI3K/AKT信号促进乳腺癌细胞的增殖、侵袭和迁移，可作为乳腺癌治疗潜在靶点。
