微小 RNA-1205 通过靶向 CDK3 调控上皮间质转化促进乳腺癌细胞转移。
MicroRNA-1205 promotes breast cancer cell metastasis by regulating epithelial-to-mesenchymal transition via targeting of CDK3.
机构信息
Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China.
Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, Shenzhen University International Cancer Center, Department of Cell Biology and Genetics, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, Guangdong 518055, PR China; Department of Pharmacy, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital (Shenzhen Institute of Translational Medicine), Shenzhen, Guangdong 518055, PR China.
出版信息
Cell Signal. 2024 Sep;121:111264. doi: 10.1016/j.cellsig.2024.111264. Epub 2024 Jun 17.
Metastasis poses a huge obstacle to the survival of breast cancer patients. The microRNA miR-1205 acts as a tumor suppressor in various cancers, but its roles in breast cancer and metastasis remain unclear. To elucidate its function in breast cancer progression, we analyzed miR-1205 expression in human tumor samples and carried out a series of functional studies in in vitro and in vivo. miR-1205 was expressed more highly in metastatic breast tumor samples than in non-metastatic samples and was associated with lymph node metastasis, clinical stage, and poor prognosis. Moreover, miR-1205 promoted breast cancer cell invasiveness in vitro and metastasis in mice by directly targeting CDK3 and reducing CDK3 protein levels. We also showed that CDK3 interacts with Snail protein, inducing Snail degradation via the ubiquitin-proteasome system and potentially affecting epithelial-to-mesenchymal transition. Furthermore, analysis of clinical tissue samples indicated that CDK3 and miR-1205 levels were inversely correlated in lymph node metastasis-positive primary tumors. This study demonstrated the pro-metastatic role of miR-1205 in breast cancer, mediated via a novel miR-1205/CDK3/Snail axis. Moreover, we identified miR-1205 and CDK3 as potential markers of invasion and progression in breast cancer.
转移是乳腺癌患者生存的巨大障碍。miR-1205 在多种癌症中作为肿瘤抑制因子发挥作用,但它在乳腺癌和转移中的作用仍不清楚。为了阐明其在乳腺癌进展中的功能,我们分析了人肿瘤样本中的 miR-1205 表达,并在体外和体内进行了一系列功能研究。miR-1205 在转移性乳腺癌样本中的表达高于非转移性样本,与淋巴结转移、临床分期和预后不良相关。此外,miR-1205 通过直接靶向 CDK3 并降低 CDK3 蛋白水平,促进体外乳腺癌细胞侵袭和小鼠转移。我们还表明 CDK3 与 Snail 蛋白相互作用,通过泛素-蛋白酶体系统诱导 Snail 降解,从而可能影响上皮-间充质转化。此外,临床组织样本分析表明,淋巴结转移阳性原发性肿瘤中 CDK3 和 miR-1205 的水平呈负相关。这项研究表明,miR-1205 在乳腺癌中具有促转移作用,是通过一个新的 miR-1205/CDK3/Snail 轴介导的。此外,我们确定 miR-1205 和 CDK3 是乳腺癌侵袭和进展的潜在标志物。