School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Department of Pharmacy, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China.
Sci Rep. 2024 Nov 18;14(1):28475. doi: 10.1038/s41598-024-77980-9.
Epithelial splicing regulatory protein 2 (ESRP2),an important alternative splicing protein of mRNA, is reported to have a dual role in tumors, which can promote or inhibit the occurrence and development of tumors. However, the function and mechanism of ESRP2 in breast cancer (BC) remain unclear. The distribution of ESRP2 expression in breast cancer and the correlation between ESRP2 expression and the overall survival rate were detected by The Cancer Genome Atlas (TCGA) database. Gene Ontology(GO)analysis, containing biological process, cellular components, and molecular function, was utilized to evaluate the potential mechanism of ESRP2 in breast cancer. The ESRP2 expression in breast cancer cell lines was detected by real-time quantitative PCR analysis (RT-qPCR) and western blotting. Cell clone was performed to examine the proliferation of ESRP2 knockdown in MCF-7 cells. The cell cycle was measured by flow cytometry assays. The role of ESRP2 knockdown in synergistic effect with chemotherapeutic agents was also determined by MTT assay. Bioinformatics analysis demonstrated that the ESRP2 gene was elevated in breast cancer cells and its overexpression was strongly correlated with shorter overall survival. GO analysis revealed that ESRP2 expression was related to cell proliferation. ESRP2 mRNA and protein expression were elevated in breast cancer cell lines, compared to the normal human breast cell line MCF-10 A. Dwon-regulation of ESRP2 inhibited cell proliferation and promoted the sensitivity of chemotherapy drug, Cisplatin(DDP) and Paclitaxel (TAXOL), in MCF-7 cells.Additionally, ESRP2 knockdown obstructed the cell cycle at the G1 phase and caused a decrease in cyclinD1 protein expression. These findings reveal that ESRP2 is highly expressed in breast cancer and is correlated with poor prognosis in breast cancer patients. ESRP2 knockdown can inhibit MCF-7 cell proliferation by arresting the cell cycle at the G1 phase and promoting the sensitivity of chemotherapy drugs (DDP and TAXOL)in MCF-7 cells. ESRP2 may be required for the regulation of breast cancer progression, as well as a critical target for the clinical treatment of breast cancer.
上皮剪接调节蛋白 2 (ESRP2) 是一种重要的 mRNA 可变剪接蛋白，据报道其在肿瘤中有双重作用，可以促进或抑制肿瘤的发生和发展。然而，ESRP2 在乳腺癌 (BC) 中的功能和机制尚不清楚。通过癌症基因组图谱 (TCGA) 数据库检测 ESRP2 表达在乳腺癌中的分布以及 ESRP2 表达与总生存率之间的相关性。利用基因本体 (GO) 分析，包括生物学过程、细胞成分和分子功能，评估 ESRP2 在乳腺癌中的潜在机制。通过实时定量 PCR 分析 (RT-qPCR) 和蛋白质印迹法检测乳腺癌细胞系中 ESRP2 的表达。进行细胞克隆以检测 MCF-7 细胞中 ESRP2 敲低对增殖的影响。通过流式细胞术检测细胞周期。还通过 MTT 测定确定 ESRP2 敲低与化疗药物协同作用的作用。生物信息学分析表明，ESRP2 基因在乳腺癌细胞中上调，其过表达与总生存率缩短密切相关。GO 分析显示 ESRP2 表达与细胞增殖有关。与正常人类乳腺细胞系 MCF-10A 相比，乳腺癌细胞系中 ESRP2 mRNA 和蛋白表达升高。ESRP2 的下调抑制细胞增殖并增强顺铂 (DDP) 和紫杉醇 (TAXOL) 化疗药物在 MCF-7 细胞中的敏感性。此外，ESRP2 敲低使细胞周期在 G1 期停滞，并导致细胞周期蛋白 D1 蛋白表达减少。这些发现表明 ESRP2 在乳腺癌中高表达，与乳腺癌患者的不良预后相关。ESRP2 敲低通过将细胞周期阻滞在 G1 期并增强 MCF-7 细胞对化疗药物 (DDP 和 TAXOL) 的敏感性来抑制 MCF-7 细胞增殖。ESRP2 可能是调节乳腺癌进展所必需的，也是乳腺癌临床治疗的关键靶点。
