Sun Kexin, Lu Tingting, Hu Cheng, Li Zhengyi, Zhu Jie, Zhang Li, Shao Xiaotong, Chen Wei
School of Medicine, Xi'an Jiaotong University, Xi'an City, Shaanxi, China; College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, China.
College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, China.
Mol Cell Probes. 2023 Apr;68:101909. doi: 10.1016/j.mcp.2023.101909. Epub 2023 Mar 16.
The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.
肺癌最常见的诊断类型和最致命的亚型是肺腺癌（LUAD）。因此，需要更详细地了解肺腺癌的潜在机制并确定其潜在靶点。越来越多的报告显示，长链非编码RNA（lncRNAs）在癌症进展中起关键作用。在本研究中，我们发现lncRNA LINC00115在LUAD组织和细胞中上调。功能研究表明，敲低LINC00115可抑制LUAD细胞的增殖、生长、侵袭和迁移。从机制上讲，我们指出miR-154-3p是LINC00115的靶标microRNA，miR-154-3p反义寡核苷酸（ASO-miR-154-3p）可部分逆转LINC00115下调对LUAD细胞的影响。进一步研究发现，特异性蛋白3（Sp3）直接与miR-154-3p相互作用，且Sp3水平与LINC00115表达呈正相关。挽救实验进一步表明，过表达Sp3可部分恢复LINC00115下调对LUAD细胞的影响。同样，体内实验证实，下调LINC00115可抑制异种移植瘤生长和Sp3表达。我们的结果表明，敲低LINC00115通过海绵吸附miR-154-3p来调节Sp3表达，从而抑制LUAD进展。这些数据表明，LINC00115/miR-154-3p/Sp3轴可能是LUAD的一个潜在治疗靶点。
