Department of Radiotherapy, Yantaishan Hospital of Yantai, Yantai, Shandong, China.
Pathol Int. 2021 Nov;71(11):741-751. doi: 10.1111/pin.13158. Epub 2021 Oct 18.
Lung adenocarcinoma (LUAD) is difficult to cureradically. Long non-coding RNAs (lncRNAs) in LUAD are a hotspot in molecular research, however, the role of lncRNA ASMTL-AS1 in LUAD is still unknown. Our study explores the role and mechanisms of ASMTL-AS1 in LUAD. Quantitative reverse transcription PCR or western blot was utilized to analyze the expression of RNAs or proteins. The influences of ASMTL-AS1 and SAT1 on LUAD cells were analyzed by functional assays. Biological instruments were applied to observe ferroptosis-related markers. In vivo assays were performed to uncover the impact of ASMTL-AS1 on LUAD. Moreover, mechanism assays were done to confirm the relationship among ASMTL-AS1, SAT1 and U2AF2. Results showed that ASMTL-AS1 was down-regulated in LUAD cells and ASMTL-AS1 up-regulation resulted in retarded LUAD cell and xenograft tumor growth along with stimulated ferroptosis. ASMTL-AS1 recruited U2AF2 to stabilize SAT1 mRNA. Furthermore, SAT1 exerted a cancer suppressor role in LUAD cells. In conclusion, we first demonstrated that ASMTL-AS1 positively regulated SAT1 to promote ferroptosis and could stabilize SAT1 mRNA via recruiting U2AF2, shedding a light on a novel molecular mechanism in LUAD progression.
肺腺癌（LUAD）很难根治。长链非编码 RNA（lncRNA）在 LUAD 中的研究是分子研究的热点，但 lncRNA ASMTL-AS1 在 LUAD 中的作用尚不清楚。本研究探讨了 ASMTL-AS1 在 LUAD 中的作用和机制。采用定量逆转录 PCR 或 Western blot 分析 RNA 或蛋白质的表达。通过功能测定分析 ASMTL-AS1 和 SAT1 对 LUAD 细胞的影响。应用生物仪器观察铁死亡相关标志物。进行体内试验以揭示 ASMTL-AS1 对 LUAD 的影响。此外，进行机制试验以确认 ASMTL-AS1、SAT1 和 U2AF2 之间的关系。结果表明，ASMTL-AS1 在 LUAD 细胞中下调，ASMTL-AS1 的上调导致 LUAD 细胞和异种移植肿瘤生长减缓，并刺激铁死亡。ASMTL-AS1 招募 U2AF2 稳定 SAT1 mRNA。此外，SAT1 在 LUAD 细胞中发挥抑癌作用。总之，我们首次证明 ASMTL-AS1 通过招募 U2AF2 正向调控 SAT1 以促进铁死亡，并能稳定 SAT1 mRNA，揭示了 LUAD 进展中的一个新的分子机制。
