N6-甲基腺苷（m6A）介导的长链非编码 RNA DLGAP1-AS1 通过 miR-299-3p/WTAP 反馈环增强乳腺癌阿霉素耐药性。
N-methyladenosine (mA)-mediated lncRNA DLGAP1-AS1enhances breast canceradriamycin resistance through miR-299-3p/WTAP feedback loop.
机构信息
Department of General Surgery, Zhangdian District People's Hospital, Zibo, China.
Department of Oncology, Zibo Central Hospital, Zibo, China.
出版信息
Bioengineered. 2021 Dec;12(2):10935-10944. doi: 10.1080/21655979.2021.2000198.
Chemotherapy resistance is identified as an obstacle for breast cancer (BC) therapy, and, besides, increasing evidence indicates that long-noncoding RNAs (lncRNAs) participate in the regulation of BC adriamycin (ADR) resistance. Here, our work shows that lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) is up-regulated in ADR-resistant BC cells (MCF-7/ADR). Clinically, higher DLGAP1-AS1 expression was closely correlated to poorer clinical prognosis. Results showed that DLGAP1-AS1 promoted the ADR IC and proliferation of ADR-resistant cells. Moreover, N-methyladenosine (mA) methyltransferase WT1 associated protein (WTAP) binds to the mA modified site of DLGAP1-AS1 and motivates its stability. Mechanistically, DLGAP1-AS1 sponged miR-299-3p through 3'-untranslated region (3'-UTR) binding, which in turn relieved the repression of WTAP and thus upregulated WTAP expression. In conclusion, above findings conclude that lncRNA DLGAP1-AS1 promotes BC ADR-resistance through WTAP/DLGAP1-AS1/miR-299-3p feedback loop.
化疗耐药被认为是乳腺癌（BC）治疗的障碍，此外，越来越多的证据表明长非编码 RNA（lncRNA）参与了 BC 阿霉素（ADR）耐药的调控。在这里，我们的工作表明，lncRNA DLGAP1 反义 RNA 1（DLGAP1-AS1）在 ADR 耐药的 BC 细胞（MCF-7/ADR）中上调。临床上，较高的 DLGAP1-AS1 表达与较差的临床预后密切相关。结果表明，DLGAP1-AS1 促进了 ADR 耐药细胞的 ADR IC 和增殖。此外，N6-甲基腺苷（mA）甲基转移酶 WT1 相关蛋白（WTAP）结合到 DLGAP1-AS1 的 mA 修饰位点，并促进其稳定性。在机制上，DLGAP1-AS1 通过 3'-非翻译区（3'-UTR）结合来海绵吸附 miR-299-3p，从而解除了 WTAP 的抑制作用，从而上调了 WTAP 的表达。总之，这些发现表明，lncRNA DLGAP1-AS1 通过 WTAP/DLGAP1-AS1/miR-299-3p 反馈环促进 BC 的 ADR 耐药性。
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