School of Medicine, South China University of Technology, Guangzhou, China.
Department of General Surgery, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China.
Bioengineered. 2022 May;13(5):13462-13473. doi: 10.1080/21655979.2022.2077893.
Increasing evidence supports that N-methyladenine (mA) and long noncoding RNAs (lncRNAs) both act as master regulators involved in breast cancer (BC) tumorigenesis at epigenetic modification level. Here, our research tries to unveil the interaction of mA and lncRNAs on BC progression and explore the underlying regulatory mechanism. In the current study, we found that LINC00667 was mA-modified lncRNA, which was up-regulated upon the overexpression of KIAA1429. The high expression of LINC00667 was correlated with the prognosis of BC patients. Bio-functional assays indicated that LINC00667 promoted the proliferation and migration of BC cells. Mechanistic assays illustrated that KIAA1429 targeted the mA modification site of LINC00667 and enhanced its mRNA stability. Moreover, LINC00667 positively regulated the KIAA1429 via sponging miR-556-5p, forming a KIAA1429/mA/LINC00667/miR-556-5p feedback loop. Collectively, the central findings of our study suggest that KIAA1429-induced LINC00667 exerted its functions as an oncogene in BC progression through mA-dependent feedback loop.
越来越多的证据表明，N6-甲基腺嘌呤（mA）和长非编码 RNA（lncRNA）都可以作为表观遗传修饰水平参与乳腺癌（BC）肿瘤发生的主要调控因子。在这里，我们的研究试图揭示 mA 和 lncRNAs 对 BC 进展的相互作用，并探讨其潜在的调控机制。在本研究中，我们发现 LINC00667 是 mA 修饰的 lncRNA，其表达水平在 KIAA1429 过表达时上调。LINC00667 的高表达与 BC 患者的预后相关。生物功能分析表明，LINC00667 促进了 BC 细胞的增殖和迁移。机制分析表明，KIAA1429 靶向 LINC00667 的 mA 修饰位点，增强其 mRNA 稳定性。此外，LINC00667 通过海绵吸附 miR-556-5p 正向调节 KIAA1429，形成 KIAA1429/mA/LINC00667/miR-556-5p 反馈环。综上所述，本研究的主要发现表明，KIAA1429 诱导的 LINC00667 通过 mA 依赖性反馈环发挥其作为 BC 进展中的癌基因的功能。
