Department of Thoracic Surgery, Beijing Aerospace General Hospital, Beijing, China.
J Biochem Mol Toxicol. 2024 Apr;38(4):e23700. doi: 10.1002/jbt.23700.
Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot. Animal experiments were performed to confirm the role of circ_0000735 in NSCLC tumorigenesis. The exosomes from cells and serum were identified using transmission electron microscopy and nanoparticle tracking analysis. We found that circ_0000735 was upregulated in NSCLC, and its knockdown repressed NSCLC cell proliferation and metastasis. In terms of mechanism, circ_0000735 targeted miR-345-5p to regulate ADAM19. MiR-345-5p inhibitor reversed the suppressive effect of circ_0000735 knockdown on NSCLC progression, and ADAM19 overexpression abolished the inhibition effect of miR-345-5p on NSCLC progression. Also, animal experiments showed that silencing of circ_0000735 reduced NSCLC tumorigenesis. In addition, exosomes mediated the intercellular transmission of circ_0000735, and serum exosomal circ_0000735 might be an important indicator for the diagnosis of NSCLC. In conclusion, circ_0000735 facilitated NSCLC progression via miR-345-5p/ADAM19 pathway, and serum exosomal circ_0000735 might be a potential biomarker for NSCLC diagnosis.
环状 RNA 是一种重要的非小细胞肺癌（NSCLC）调控因子。已经发现环状 RNA_0000735 在 NSCLC 组织中显著过表达。因此，需要进一步探索其在 NSCLC 进展中的作用和机制。采用实时定量 PCR 测定 circ_0000735、miR-345-5p 和解整合素金属蛋白酶 19（ADAM19）的表达水平。利用 EDU 染色、划痕愈合和 Transwell 实验检测细胞增殖和转移。采用 Western blot 测定转移标志物、外泌体标志物和 ADAM19 的蛋白水平。进行动物实验以证实 circ_0000735 在 NSCLC 肿瘤发生中的作用。通过透射电子显微镜和纳米颗粒跟踪分析鉴定细胞和血清中的外泌体。我们发现 circ_0000735 在 NSCLC 中上调，其敲低抑制 NSCLC 细胞增殖和转移。就机制而言，circ_0000735 靶向 miR-345-5p 以调节 ADAM19。miR-345-5p 抑制剂逆转了 circ_0000735 敲低对 NSCLC 进展的抑制作用，而 ADAM19 过表达消除了 miR-345-5p 对 NSCLC 进展的抑制作用。此外，动物实验表明沉默 circ_0000735 可降低 NSCLC 肿瘤的发生。此外，外泌体介导了 circ_0000735 的细胞间传递，血清外泌体 circ_0000735 可能是 NSCLC 诊断的重要指标。总之，circ_0000735 通过 miR-345-5p/ADAM19 通路促进 NSCLC 进展，血清外泌体 circ_0000735 可能是 NSCLC 诊断的潜在生物标志物。
