Liu Wei-Wei, Li Wei-Dong, Zhang Yan-Ju, Zhang Man-Li
Breast Center, Cangzhou People's Hospital, Cangzhou 061000, Hebei Province, People's Republic of China.
Cancer Manag Res. 2021 Jan 18;13:439-447. doi: 10.2147/CMAR.S284277. eCollection 2021.
To explore the regulatory role of miR497-5p- axis in triple-negative breast cancer (TNBC) cells and its predictive value for early diagnosis.
Cancer tissue and adjacent tissue samples were collected from 86 patients with TNBC.RT-PCR was used to detect the expression of miR497-5p and (target gene) mRNA, determined by biological prediction in tissue and TNBC cells. ROC was used to analyze the diagnostic value of miR497-5p in TNBC. MTT, invasion, and flow cytometry were used to detect the proliferation, invasion, cycle, apoptosis rate, and expression of related proteins of TNBC cells with overexpression of miR497-5p or knockdown of .
RT-qPCR results showed that miR497-5p levels were significantly downregulated in TNBC tissue and cells, while CCNE1 expression was significantly upregulated, and miR497-5p expression was negatively correlated with that of CCNE1 (<0.001). ROC analysis showed that the AUC of miR497-5p for TNBC was >0.9, which had better diagnostic value. The cell tests revealed that miR497-5p played a role in tumor inhibition, including inhibiting proliferation and invasion of TNBC cells, blocking the cell cycle, and promoting apoptosis. Bioinformatic prediction and subsequent experiments revealed that was the direct target of miR497-5p. Furthermore, after knocking down the expression of in TNBC cells, the proliferation and invasion of TNBC cells were significantly inhibited, the cell cycle blocked, and the apoptosis rate significantly increased (<0.001), and expression of the proapoptosis-related proteins Bax and caspase 3 (cleaved) were upregulated, while expression of the antiapoptosis-related protein BCL2 was downregulated (<0.001).
miR497-5p inhibited the proliferation and invasion of TNBC cells by targeting CCNE1, blocked the cell cycle and promoted the apoptosis of TNBC cells, and had better diagnostic value for TNBC. miR497-5p can be used as a new potential target for the treatment of TNBC.
探讨miR497-5p轴在三阴性乳腺癌（TNBC）细胞中的调控作用及其对早期诊断的预测价值。
收集86例TNBC患者的癌组织及癌旁组织样本。采用RT-PCR检测miR497-5p和（靶基因）mRNA的表达，通过组织及TNBC细胞中的生物学预测确定。采用ROC分析miR497-5p在TNBC中的诊断价值。采用MTT、侵袭实验和流式细胞术检测过表达miR497-5p或敲低（靶基因）的TNBC细胞的增殖、侵袭、细胞周期、凋亡率及相关蛋白表达。
RT-qPCR结果显示，TNBC组织和细胞中miR497-5p水平显著下调，而CCNE1表达显著上调，且miR497-5p表达与CCNE1呈负相关（<0.001）。ROC分析显示，miR497-5p对TNBC的AUC>0.9，具有较好的诊断价值。细胞实验表明，miR497-5p发挥肿瘤抑制作用，包括抑制TNBC细胞的增殖和侵袭、阻断细胞周期及促进凋亡。生物信息学预测及后续实验表明，（靶基因）是miR497-5p的直接靶点。此外，敲低TNBC细胞中（靶基因）的表达后，TNBC细胞的增殖和侵袭显著受抑制，细胞周期阻断，凋亡率显著增加（<0.001），促凋亡相关蛋白Bax和caspase 3（裂解型）表达上调，而抗凋亡相关蛋白BCL2表达下调（<0.001）。
miR497-5p通过靶向CCNE1抑制TNBC细胞的增殖和侵袭，阻断细胞周期并促进TNBC细胞凋亡，对TNBC具有较好的诊断价值。miR497-5p可作为TNBC治疗的新潜在靶点。
