Shanghai Key Laboratory of Molecular Imaging, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, 201318, People's Republic of China.
Department of Clinical Lab, Shanghai Health Commission Key Lab of Artificial Intelligence (AI)-Based Management of Inflammation and Chronic Diseases, Sino-French Cooperative Central Lab, Shanghai Pudong Gongli Hospital, Secondary Military Medical University, Shanghai, 200135, People's Republic of China.
Respir Res. 2023 Apr 3;24(1):100. doi: 10.1186/s12931-023-02378-6.
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.
环状 RNA（circRNAs）是一类新的丰富的调控 RNA，在多种类型的癌症中发挥作用。虽然 hsa_circ_0046701（circ-YES1）在非小细胞肺癌（NSCLC）中的功能尚不清楚。
检测了正常肺上皮细胞和 NSCLC 细胞中 circ-YES1 的表达。制备了 circ-YES1 的小干扰 RNA，评估了细胞增殖和迁移。在裸鼠中进行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基因实验鉴定 circ-YES1 的下游靶标。
与正常肺上皮细胞相比，circ-YES1 在 NSCLC 细胞中表达增加，circ-YES1 敲低后细胞增殖和迁移受到抑制。高迁移率族蛋白 B1（HMGB1）和 miR-142-3p 被发现是 circ-YES1 的下游靶标，miR-142-3p 抑制和 HMGB1 过表达逆转了 circ-YES1 敲低对细胞增殖和迁移的影响。同样，HMGB1 过表达逆转了 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 敲低抑制了裸鼠异种移植模型中的肿瘤发展和转移。
综上所述，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 作为 NSCLC 治疗新靶点的开发。
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