LINC00094/miR-19a-3p/CYP19A1轴通过EMT途径影响ER阳性乳腺癌细胞对来曲唑的敏感性

Yuan Xiang, Hui Liu, Hao Hu, Leping Li, Qiang Zong, Tangwei Wu, Xiaoyi Li, Shiqiang Fang, Yi-Wen Liu, Y. Zhan, Hui Wang, Zhongxin Lu
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引用次数: 6

摘要

乳腺癌的内分泌治疗耐药是目前治疗中亟待解决的难点和挑战。本研究通过RT-QPCR、Western Blot、荧光素酶测定、免疫荧光和药敏试验检测非编码RNA LINC00094和miR-19a-3p在体内和体外对乳腺癌的影响。乳腺癌耐药患者血浆CYP19A1水平低于药物敏感患者。与正常受试者相比,乳腺癌患者血浆中miR-19a-3p的表达水平较高。miR-19a-3p在雌激素受体阳性乳腺癌细胞中高表达。miR-19a-3p的表达促进乳腺癌细胞的迁移和EMT,降低乳腺癌对来曲唑的敏感性。LINC00094海绵吸附miR-19a-3p。LINC00094促进miR-19a-3p靶基因CYP19A1的表达,抑制乳腺癌的EMT过程,最终促进er阳性乳腺癌细胞对来曲唑的敏感性。本研究发现了雌激素受体阳性乳腺癌来曲唑敏感性的新机制。
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LINC00094/miR-19a-3p/CYP19A1 axis affects the sensitivity of ER positive breast cancer cells to Letrozole through EMT pathway
The endocrine therapy resistance of breast cancer is the difficulty and challenge to be urgently solved in the current treatment. In this study, we examined the effects of noncoding RNA LINC00094 and miR-19a-3p on breast cancer in vivo and in vitro by RT-QPCR, Western Blot, luciferase assay, immunofluorescence and drug sensitivity tests. The plasma level of CYP19A1 in patients with breast cancer resistance was lower than that in drug sensitive patients. Compared with normal subjects, miR-19a-3p was highly expressed in plasma of patients with breast cancer. miR-19a-3p is highly expressed in estrogen receptor positive breast cancer cells. The expression of miR-19a-3p promoted the migration and EMT of breast cancer cells and reduced the sensitivity of breast cancer to Letrozole. LINC00094 sponge adsorbed miR-19a-3p. LINC00094 promotes the expression of CYP19A1, the target gene of miR-19a-3p, and inhibits the EMT process of breast cancer, ultimately promoting the sensitivity of ER-positive breast cancer cells to Letrozole. This study found a new mechanism of Letrozole sensitivity in ER positive breast cancer.
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