Xu Linfei, Lin Yongfeng, Zhang Liming, Lin Xingzhang, Liu Sheng
Department of Urology, Taizhou Municipal Hospital (Taizhou University Affiliated Municipal Hospital), School of Medicine, Taizhou University, No, 581 East of Shifu Avenue, Jiaojiang District, Taizhou City, 318000, Zhejiang Province, China.
J Mol Histol. 2025 Jul 9;56(4):220. doi: 10.1007/s10735-025-10510-7.
Long non-coding RNA MINCR performs a tumor-promoting role in various cancers. Accordingly, this research analyzed whether MINCR exerted tumor-promoting effects and facilitated gemcitabine (GEM) resistance in BC. MINCR, microRNA (miR)-876-5p, ZEB1, and PHGDH expression was detected in BC tissues and cells. Following the construction of GEM-resistant cells, MINCR expression was examined with RT-qPCR. Gain- and loss-of-function assays were conducted in GEM-resistant cells, followed by the measurement of cell proliferation, invasion, and apoptosis. The relationships among MINCR, miR-876-5p, and ZEB1 were assessed with dual-luciferase and RIP assays. Subcutaneous tumor formation in nude mice was conducted for in vivo corroboration. MINCR was up-regulated in BC tissues and cells and GEM-resistant BC cells. miR-876-5p expression was poor and ZEB1 and PHGDH expression was abundant in BC tissues. Mechanistically, MINCR enhanced ZEB1 expression in BC cells via competitive binding to miR-876-5p, and ectopic ZEB1 induced PHGDH up-regulation. MINCR silencing diminished proliferation and invasion while accelerating apoptosis in GEM-resistant BC cells, which was further advanced by miR-876-5p overexpression but nullified by ZEB1 overexpression. Meanwhile, MINCR silencing or miR-876-5p overexpression synergized with GEM to depress BC growth in vivo. MINCR silencing impedes GEM resistance in BC through the miR-876-5p/ZEB1/PHGDH axis.
长链非编码RNA MINCR在多种癌症中发挥促肿瘤作用。因此，本研究分析了MINCR是否在乳腺癌中发挥促肿瘤作用并促进吉西他滨（GEM）耐药。检测了乳腺癌组织和细胞中MINCR、微小RNA（miR）-876-5p、锌指E盒结合蛋白1（ZEB1）和磷酸甘油酸脱氢酶（PHGDH）的表达。构建GEM耐药细胞后，用逆转录定量聚合酶链反应检测MINCR表达。在GEM耐药细胞中进行功能获得和缺失实验，随后测量细胞增殖、侵袭和凋亡。用双荧光素酶和RNA免疫沉淀实验评估MINCR、miR-876-5p和ZEB1之间的关系。在裸鼠中进行皮下肿瘤形成实验以进行体内验证。MINCR在乳腺癌组织和细胞以及GEM耐药的乳腺癌细胞中上调。miR-876-5p在乳腺癌组织中表达较低，而ZEB1和PHGDH表达丰富。机制上，MINCR通过与miR-876-5p竞争性结合增强乳腺癌细胞中ZEB1的表达，异位表达的ZEB1诱导PHGDH上调。MINCR沉默减少了GEM耐药乳腺癌细胞的增殖和侵袭，同时加速了细胞凋亡，miR-876-5p过表达进一步增强了这种作用，但ZEB1过表达使其抵消。同时，MINCR沉默或miR-876-5p过表达与GEM协同抑制体内乳腺癌生长。MINCR沉默通过miR-876-5p/ZEB1/PHGDH轴阻碍乳腺癌中的GEM耐药。
