Department of Respiratory, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, 314000, Zhejiang, People's Republic of China.
Jiaxing Key Laboratory of Precision Treatment for Lung Cancer, the First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, 314000, Zhejiang, People's Republic of China.
Environ Sci Pollut Res Int. 2023 May;30(24):65237-65249. doi: 10.1007/s11356-023-26307-8. Epub 2023 Apr 20.
The eukaryotic translation initiation factor 4A (eIF4A) family determines transcription efficiency by directly binding to precursor RNAs. One member, EIF4A3, modulates the expression of circRNAs. Circular RNA SCAP (circSCAP), a newly found circRNA, has been implicated in atherosclerosis. Yet, how circSCAP regulates cancer development and progression remains understudied. Here, we investigated the function of circSCAP and the molecular mechanism in the tumorigenesis and progression of non-small-cell lung cancer (NSCLC). CircSCAP was upregulated in both NSCLC tissues and cell lines and was mainly located in the cytoplasm. CircSCAP expression was promoted by EIF4A3, which was associated with poor prognosis in patients with NSCLC. CircSCAP sponged miR-7 to upregulate small mothers against decapentaplegic 2 (SMAD2). CircSCAP knockdown undermined cell proliferation, migration, and invasion abilities in NSCLC cell lines (SPCA1 and A549), which was rescued by either inhibiting miR-7 or overexpressing SMAD2. Moreover, circSCAP knockdown upregulated E-cadherin, while downregulating N-cadherin, Vimentin, and MMP9 in SPCA1 and A549 cells, which were abolished by either inhibiting miR-7 or overexpressing SMAD2. Additionally, miR-7 was markedly downregulated, whereas SMAD2 was significantly upregulated in NSCLC tissues. MiR-7 expression was inversely correlated with circSCAP and SMAD2 expression in NSCLC tissues. In conclusion, this study demonstrates that circSCAP is significantly upregulated in NSCLC cell lines and tissues and elucidates that circSCAP facilitates NSCLC progression by sponging miR-7 and upregulating SMAD2. The study provides a novel molecular target for early diagnosis and treatment of NSCLC.
真核翻译起始因子 4A（eIF4A）家族通过直接结合前体 RNA 来决定转录效率。其中一个成员 EIF4A3 调节 circRNA 的表达。CircRNA SCAP（circSCAP）是一种新发现的 circRNA，与动脉粥样硬化有关。然而，circSCAP 如何调节癌症的发生和发展仍研究甚少。在这里，我们研究了 circSCAP 的功能及其在非小细胞肺癌（NSCLC）发生和发展中的分子机制。CircSCAP 在 NSCLC 组织和细胞系中均上调，主要位于细胞质中。EIF4A3 促进 circSCAP 的表达，与 NSCLC 患者的预后不良相关。CircSCAP 通过海绵吸附 miR-7 来上调小 mothers against decapentaplegic 2（SMAD2）。CircSCAP 敲低削弱了 NSCLC 细胞系（SPCA1 和 A549）的增殖、迁移和侵袭能力，这一作用可被 miR-7 抑制或 SMAD2 过表达所挽救。此外，CircSCAP 敲低在上皮-间质转化标志物 E-cadherin 表达上调的同时，下调 N-cadherin、Vimentin 和 MMP9 的表达，这一作用可被 miR-7 抑制或 SMAD2 过表达所废除。此外，在 NSCLC 组织中，miR-7 的表达显著下调，而 SMAD2 的表达显著上调。在 NSCLC 组织中，miR-7 的表达与 circSCAP 和 SMAD2 的表达呈负相关。总之，本研究表明 circSCAP 在 NSCLC 细胞系和组织中显著上调，并阐明 circSCAP 通过海绵吸附 miR-7 和上调 SMAD2 促进 NSCLC 进展。该研究为 NSCLC 的早期诊断和治疗提供了新的分子靶点。
