Department of Medical Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 430014, Hubei, P.R. China.
Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, 430081, Hubei, P.R. China.
Aging (Albany NY). 2022 Jun 2;14(11):4755-4768. doi: 10.18632/aging.204110.
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 and 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.
乳腺癌的内分泌治疗耐药是当前治疗中亟待解决的难点和挑战。本研究通过 RT-QPCR、Western blot、荧光素酶报告基因实验、免疫荧光和药物敏感性实验，探讨了非编码 RNA LINC00094 和 miR-19a-3p 对乳腺癌的影响。乳腺癌耐药患者的血浆 CYP19A1 水平低于药物敏感患者。与正常受试者相比，miR-19a-3p 在乳腺癌患者的血浆中高表达。miR-19a-3p 在雌激素受体阳性乳腺癌细胞中高表达。miR-19a-3p 的表达促进了乳腺癌细胞的迁移和 EMT，并降低了乳腺癌对来曲唑的敏感性。LINC00094 可吸附 miR-19a-3p。LINC00094 促进 miR-19a-3p 的靶基因 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 ER 阳性乳腺癌中来曲唑敏感性的新机制。
