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Inhibition of breast cancer cell proliferation with anti-microRNA oligonucleotides flanked by interstrand cross-linked duplexes
Nucleosides, Nucleotides & Nucleic Acids ( IF 1.3 ) Pub Date : 2019-10-04 , DOI: 10.1080/15257770.2019.1671595
Sho Okumura 1, 2, 3 , Yu Hirano 1, 3 , Yasuo Komatsu 1, 4
Affiliation  

Abstract Breast cancer is the most frequent cancer affecting women worldwide. Traditional chemotherapy, hormone therapy, and targeted therapy are used for breast cancer treatment. However, breast cancer is a heterogeneous disease, and patients often develop drug resistance. Therefore, various new therapeutic strategies have been investigated, including microRNA regulation. Anti-microRNA oligonucleotides (AMOs) are one of the most potent agents in oligonucleotide therapy. The inhibition activity of an AMO can be increased by flanking its single-stranded antisense sequence (the widely used structure for AMOs) with interstrand cross-linked duplexes (CLDs). An extrastable CLD improves nuclease resistance and stabilizes hybridization with a target. This study investigated the effects of anti-microRNA-21 (miR-21) AMO modified with CLDs on breast cancer cells without using reporter assay. The CLD-modified AMO suppressed breast cancer cell proliferation for a long duration compared to other types of AMOs. In addition, it expectedly up-regulated the miR-21-controlled expression of tumor suppressor genes. Therefore, an AMO flanked by CLDs can be a promising strategy for breast cancer treatment.

中文翻译:

侧接链间交联双链体的抗微RNA寡核苷酸抑制乳腺癌细胞增殖

摘要 乳腺癌是影响全球女性的最常见癌症。传统的化疗、激素治疗和靶向治疗用于乳腺癌治疗。然而,乳腺癌是一种异质性疾病,患者往往会产生耐药性。因此,已经研究了各种新的治疗策略,包括 microRNA 调节。抗微小 RNA 寡核苷酸 (AMO) 是寡核苷酸治疗中最有效的药物之一。AMO 的抑制活性可以通过将其单链反义序列(广泛使用的 AMO 结构)与链间交联双链体 (CLD) 侧翼连接来增加。超稳定 CLD 可提高核酸酶抗性并稳定与目标的杂交。本研究在不使用报告基因检测的情况下研究了经 CLD 修饰的抗 microRNA-21 (miR-21) AMO 对乳腺癌细胞的影响。与其他类型的 AMO 相比,CLD 修饰的 AMO 可长时间抑制乳腺癌细胞增殖。此外,它有望上调 miR-21 控制的肿瘤抑制基因的表达。因此,侧翼为 CLD 的 AMO 可能是一种很有前景的乳腺癌治疗策略。
更新日期:2019-10-04
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