首页> 外国专利> LY6K miR-192-5p Compositions supportive for treating drug-resistanced breast cancer containing LY6K expression inhibitors or miR-192-5p inhibitors

LY6K miR-192-5p Compositions supportive for treating drug-resistanced breast cancer containing LY6K expression inhibitors or miR-192-5p inhibitors

机译:LY6K miR-192-5p含有LY6K表达抑制剂或miR-192-5p抑制剂的抗药性乳腺癌组合物

摘要

The present invention relates to an anticancer drug-resistant breast cancer adjuvant comprising LY6K expression inhibitor or miR-192-5p inhibitor. The present invention discloses the mechanism of resistance to antihormonal drugs such as tamoxifen, which is a breast cancer therapeutic agent, 192-5 inhibition restores tamoxifen sensitivity by ERα re-expression, and provides a method of inhibiting the anticancer drug resistance and restoring the sensitivity to the anticancer drug. ERα is a clinically important therapeutic target in breast cancer. However, ERa loss causes tolerance to anti-estrogen drugs such as tamoxifen. The present inventors have found that LY6K associated with breast cancer cell proliferation and metastasis has an inverse correlation with ERa. ERα expression was down-regulated when LY6K was overexpressed in MCF-7 and T47D cells expressing ERα. In addition, we have shown that miR-192-5p targeting the 3'UTR of ESR1 in breast cancer is induced by LY6K gene expression. Luciferase assay revealed that miR-192-5p is regulated by LY6K and binds directly to the 3'UTR of ERa. In addition, miR-192-5p inhibition in LY6K-overexpressing cells restored tamoxifen sensitivity by re-expression of ERa. Thus, miR-192-5p, which is regulated by LY6K in breast cancer, inhibits ERα expression and endocrine resistance. Taken together, LY6K can play an important role in anticancer drug resistance through the suppression of ERα expression.
机译:本发明涉及包含LY6K表达抑制剂或miR-192-5p抑制剂的抗癌抗药性乳腺癌佐剂。本发明公开了对乳腺癌治疗药物他莫昔芬等抗激素药的耐药机制,通过ERα的重新表达,192-5抑制作用恢复了他莫昔芬的敏感性,并提供了一种抑制抗癌药耐药性并恢复敏感性的方法。去抗癌药。 ERα是乳腺癌的临床重要治疗靶标。但是,ERa丢失会引起对他莫昔芬等抗雌激素药物的耐受性。本发明人已经发现,与乳腺癌细胞增殖和转移相关的LY6K与ERa成反比。当LY6K在表达ERα的MCF-7和T47D细胞中过表达时,ERα的表达下调。此外,我们已经证明,LY6K基因表达可诱导靶向ESR1的3'UTR的miR-192-5p。萤光素酶测定显示,miR-192-5p受LY6K调控,并直接与ERa的3'UTR结合。此外,在LY6K过表达的细胞中,miR-192-5p的抑制作用通过重新表达ERa恢复了他莫昔芬的敏感性。因此,在乳腺癌中受到LY6K调节的miR-192-5p抑制ERα表达和内分泌抵抗力。两者合计,LY6K可通过抑制ERα表达在抗癌药物耐药性中发挥重要作用。

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