Wang Shou-Man, Pang Jian, Zhang Ke-Jing, Zhou Zhi-Yang, Chen Fei-Yu
Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China.
Clinical Research Center for Breast Cancer in Hunan Province, Changsha 410008, Hunan Province, P.R. China.
Mol Ther Oncolytics. 2021 Mar 17;21:62-73. doi: 10.1016/j.omto.2021.03.009. eCollection 2021 Jun 25.
Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study investigated the molecular mechanism and influences of MIR503HG, miR-224-5p, and homeobox A9 (HOXA9) on TNBC cell growth and migration. Dual-luciferase reporter gene and RNA immunoprecipitation were performed to examine the regulation of MIR503HG, miR-224-5p, and HOXA9. Cell proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays. Finally, nude mice were employed to investigate the influence of MIR503HG on TNBC tumor growth. HOXA9 protein levels were detected by immunohistochemical staining. MIR503HG and HOXA9 expression were reduced in TNBC, while miR-224-5p was increased. Overexpression of MIR503HG or HOXA9 reduced the cell migration ability and proliferation and promoted apoptosis, and knockdown of MIR503HG or overexpression of miR-224-5p exhibited the opposite effects. Furthermore, MIR503HG promoted HOXA9 expression by inhibiting miR-224-5p. Overexpression of miR-224-5p reversed the effects of MIR503HG overexpression on TNBC cells, while overexpression of HOXA9 reversed the effect of MIR503HG knockdown. Additionally, an study proved that MIR503HG inhibited TNBC tumor growth via the miR-224-5p/HOXA9 axis. MIR503HG inhibited cell proliferation and promoted the apoptosis of TNBC cells via the miR-224-5p/HOXA9 axis, which may function as a novel target for the treatment of TNBC.
三阴性乳腺癌(TNBC)是一种侵袭性很强的乳腺癌亚型。本研究探讨了MIR503HG、miR-224-5p和同源盒A9(HOXA9)对TNBC细胞生长和迁移的分子机制及影响。进行双荧光素酶报告基因实验和RNA免疫沉淀实验以检测MIR503HG、miR-224-5p和HOXA9之间的调控关系。通过集落形成实验、流式细胞术和Transwell实验评估细胞增殖、凋亡、迁移和侵袭能力。最后,利用裸鼠研究MIR503HG对TNBC肿瘤生长的影响。通过免疫组化染色检测HOXA9蛋白水平。TNBC中MIR503HG和HOXA9表达降低,而miR-224-5p表达增加。MIR503HG或HOXA9过表达降低细胞迁移能力和增殖并促进凋亡,而MIR503HG敲低或miR-224-5p过表达则表现出相反的效果。此外,MIR503HG通过抑制miR-224-5p促进HOXA9表达。miR-224-5p过表达逆转了MIR503HG过表达对TNBC细胞的影响,而HOXA9过表达逆转了MIR503HG敲低的影响。另外,一项研究证明MIR503HG通过miR-224-5p/HOXA9轴抑制TNBC肿瘤生长。MIR503HG通过miR-224-5p/HOXA9轴抑制TNBC细胞增殖并促进其凋亡,这可能成为治疗TNBC的新靶点。