Clinical Laboratory, Linyi People's Hospital, Linyi, China.
Department of Thoracic Surgery, Fenghuangling Street Health Hospital, Linyi, China.
J Cell Physiol. 2020 Oct;235(10):6684-6696. doi: 10.1002/jcp.29564. Epub 2020 Jan 31.
Long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in tumorigenesis. lncRNA LINC01561 (LINC01561) is a newly identified tumor-related lncRNA and its dysregulation has been demonstrated in several tumors. However, whether LINC01561 is involved in the progression of non-small-cell lung carcinoma (NSCLC) and its underlying mechanisms remain unknown. In this study, we first provided evidence that LINC01561 expressions were distinctly upregulated in NSCLC tissues and cell lines. Combining with bioinformatics assays and mechanism experiments, our group demonstrated that LINC01561 was activated by SOX2 in NSCLC. Clinical research revealed that upregulation of LINC01561 was related to poorer clinicopathologic features and shorter survival time. Functionally, suppression of LINC01561 exhibited tumor-suppressive functions through impairing cell proliferation, migration, and invasion as well as inducing apoptosis. Moreover, we verified that LINC01561 could directly bind to miR-760, isolating miR-760 from its target gene SHC SH2 domain-binding protein 1 (SHCBP1). We also found that SHCBP1 was lowly expressed in NSCLC and served as a tumor promoter. A functional study indicated that LINC01561 regulated SHCBP1 expression by competitively binding to miR-760. In summary, our findings indicated that SOX2-induced overexpression of LINC01561 promoted the proliferation and metastasis by acting as a competing endogenous RNA to modulate SHCBP1 by sponging miR-760.
长链非编码 RNA(lncRNAs)已被证明在肿瘤发生中具有关键的调节作用。lncRNA LINC01561(LINC01561)是一种新鉴定的肿瘤相关 lncRNA,其失调已在几种肿瘤中得到证实。然而,LINC01561 是否参与非小细胞肺癌(NSCLC)的进展及其潜在机制尚不清楚。在这项研究中,我们首先提供了证据表明 LINC01561 在 NSCLC 组织和细胞系中表达明显上调。结合生物信息学分析和机制实验,我们小组证明 LINC01561 在 NSCLC 中由 SOX2 激活。临床研究表明,LINC01561 的上调与较差的临床病理特征和较短的生存时间有关。功能上,抑制 LINC01561 通过损害细胞增殖、迁移和侵袭以及诱导细胞凋亡来发挥肿瘤抑制作用。此外,我们验证了 LINC01561 可以直接与 miR-760 结合,将 miR-760 从其靶基因 SHC SH2 结构域结合蛋白 1(SHCBP1)中分离出来。我们还发现,SHCBP1 在 NSCLC 中低表达,起肿瘤促进剂的作用。功能研究表明,LINC01561 通过竞争性结合 miR-760 调节 SHCBP1 的表达。总之,我们的研究结果表明,SOX2 诱导的 LINC01561 过表达通过作为竞争性内源性 RNA 来调节 SHCBP1,通过海绵吸附 miR-760 来促进 NSCLC 的增殖和转移。