Liang Yaning, Shi Cuiyu, Wang Yu, Fan Bingjie, Song Wei, Shen Rong
Department of Minimally Invasive Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Sci Rep. 2024 Dec 30;14(1):32135. doi: 10.1038/s41598-024-83938-8.
Nowadays, the investigation for overcoming tamoxifen (TAM) resistance is confronting a considerable challenge. Therefore, immediate attention is required to elucidate the mechanism underlying TAM resistance in breast cancer. This research primarily aimed to define how miRNA-363-3p facilitates resistance to TAM in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and TAM-resistant MCF-7 cells (MCF-7-TAM). An increase in miRNA-363-3p levels was observed in MCF-7-TAM cells. In MCF-7 cells, miRNA-363-3p directly targeted and negatively regulated phosphatase and tensin homolog (PTEN). Reduction of miRNA-363-3p retarded cell growth and accelerated cell apoptosis, thereby enhancing the sensitivity of TAM. Moreover, analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed significant enrichment of target genes within the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Ultimately, miR-363-3p decreased the responsiveness of breast cancer cells to TAM by targeting and suppressing PTEN through a mechanism associated with the PI3K-Akt pathway. Therefore, these results suggest that miR-363-3p-dependent PTEN expression contributes to the mechanisms underlying breast cancer endocrine resistance.
如今，克服他莫昔芬（TAM）耐药性的研究面临着巨大挑战。因此，需要立即关注以阐明乳腺癌中TAM耐药的潜在机制。本研究主要旨在确定miRNA-363-3p如何促进乳腺癌对TAM的耐药性。使用从乳腺癌MCF-7细胞和耐TAM的MCF-7细胞（MCF-7-TAM）制备的RNA进行高通量miRNA测序。在MCF-7-TAM细胞中观察到miRNA-363-3p水平升高。在MCF-7细胞中，miRNA-363-3p直接靶向并负调控磷酸酶和张力蛋白同源物（PTEN）。miRNA-363-3p的减少会抑制细胞生长并加速细胞凋亡，从而增强对TAM的敏感性。此外，使用京都基因与基因组百科全书（KEGG）通路分析显示，磷酸肌醇-3-激酶（PI3K）/蛋白激酶B（AKT）信号通路中的靶基因显著富集。最终，miR-363-3p通过与PI3K-Akt通路相关的机制靶向并抑制PTEN，从而降低乳腺癌细胞对TAM的反应性。因此，这些结果表明miR-363-3p依赖的PTEN表达有助于乳腺癌内分泌耐药的潜在机制。
