Long noncoding RNA SBF2 antisense RNA 1 (lncRNA SBF2-AS1) has been reported to be involved in non-small-cell lung cancer (NSCLC) tumorigenesis. However, the biological role and regulatory mechanism of lncRNA SBF2-AS1 on NSCLC metastasis remain largely unknown. In this study, the expression level and functional role of SBF2-AS1 were investigated in both NSCLC tissues and cell lines. We found that SBF2-AS1 was upregulated in both NSCLC tissues and cell lines. Patients with high levels of SBF2-AS1 have larger tumors, higher malignancy, and poor prognosis. Knockdown of SBF2-AS1 significantly inhibited tumor growth in vivo and cell proliferation, migration, and invasion in vitro. Moreover, bioinformatics analysis, chromatin immunoprecipitation assay, and luciferase reporter assay proved that the upregulation of SBF2-AS1 was mediated by transcription factor E2F1. Further experiments demonstrated that miR-362-3p had complementary binding site with 3′-UTR of SBF2-AS1. Besides, luciferase reporter assay validated that GRB2 was the target protein of miR-362-3p. Rescue experiments showed that SBF2-AS1 silencing inhibited cell invasion and migration, while cotransfection si-SBF2-AS1 and miR-362-3p inhibitor rescued the effect of si-SBF2-AS1. These results demonstrate that E2F1-induced overexpression of SBF2-AS1 promotes the expression of GRB2 by targeting miR-362-3p to facilitate the metastasis of NSCLC.

中文翻译：

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E2F1诱导的长非编码RNA SBF2-AS1的过表达通过调节miR-362-3p / GRB2轴促进非小细胞肺癌转移。

据报道，长非编码RNA SBF2反义RNA 1（lncRNA SBF2-AS1）参与非小细胞肺癌（NSCLC）的肿瘤发生。然而，lncRNA SBF2-AS1对NSCLC转移的生物学作用和调控机制仍然未知。在这项研究中，研究了SBF2-AS1在NSCLC组织和细胞系中的表达水平和功能作用。我们发现SBF2-AS1在NSCLC组织和细胞系中均被上调。SBF2-AS1水平高的患者肿瘤更大，恶性程度更高且预后不良。敲低SBF2-AS1显著抑制肿瘤生长的体内和细胞的增殖，迁移和侵袭体外。此外，生物信息学分析，染色质免疫沉淀测定和荧光素酶报告基因测定证明，SBF2-AS1的上调是由转录因子E2F1介导的。进一步的实验表明，miR-362-3p与SBF2-AS1的3'-UTR具有互补的结合位点。此外，荧光素酶报告基因检测证实GRB2是miR-362-3p的靶蛋白。救援实验表明，SBF2-AS1沉默可抑制细胞侵袭和迁移，而共转染si-SBF2-AS1和miR-362-3p抑制剂可挽救si-SBF2-AS1的作用。这些结果表明，E2F1诱导的SBF2-AS1过表达通过靶向miR-362-3p促进NSCLC的转移而促进GRB2的表达。