Circular RNAs（circRNAs）是一类丰富的调节性RNA，其在各种癌症中具有不同作用。虽然hsa_circ_0046701（circ-YES1）在非小细胞肺癌(NSCLC)中的功能尚不明确，但对circ-YES1在正常肺上皮细胞和NSCLC细胞中的表达进行了研究。制备了circ-YES1的小干扰RNA（siRNA），评估了细胞增殖和迁移。进行裸鼠肿瘤发生实验以验证circ-YES1的作用。利用生物信息学分析和荧光素酶报告试验鉴定circ-YES1的下游靶标。与正常肺上皮细胞相比，NSCLC细胞中circ-YES1的表达增加，circ-YES1敲除后细胞增殖和迁移受到抑制。发现高迁移率族蛋白B1（HMGB1）和miR-142-3p都是circ-YES1的下游靶标，并且miR-142-3p抑制和HMGB1过表达可以反转circ-YES1敲除对细胞增殖和迁移的影响。同样，HMGB1的过表达可以反转miR-142 -3p过表达对这两个过程的影响。成像实验结果表明，circ-YES1敲除阻碍了裸鼠异种移植模型中的肿瘤发生和转移。总的来说，我们的结果表明，circ-YES1通过miR-142-3p-HMGB1轴促进肿瘤发展，并支持将circ-YES1转化为新的NSCLC治疗靶点。© 2023. The Author（s）。

Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa_circ_0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear.Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1.Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model.Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p-HMGB1 axis and support the development of circ-YES1 probability as a new therapeutic NSCLC target.© 2023. The Author(s).