Department of Respiratory Medicine, Minhang Hospital, Fudan University, China.
Department of Emergency Medicine, Minhang Hospital, Fudan University, China.
Biomed Res Int. 2020 Sep 9;2020:5307641. doi: 10.1155/2020/5307641. eCollection 2020.
The incidence and mortality of lung cancer were extremely high. The present study showed that SRCIN1 was an oncogene in non-small-cell lung cancer (NSCLC). Public dataset analysis showed SRCIN1 was significantly overexpressed in NSCLC samples. Also, we found that NSCLC patients with higher SRCIN1 expression had shorter OS time by analyzing TCGA, Kaplan-Meier Plotter, GSE30219, GSE50081, and GSE19188 databases. Overexpression or knockdown of SRCIN1 significantly induced or reduced A549 and H1299 cell proliferation. Furthermore, we found SRCIN1 was directly targeted by miR-211. Overexpression or knockdown of miR-211 suppressed or induced SRCIN1 levels in NSCLC. Moreover, we found that miR-211 affected NSCLC cell proliferation through SRCIN1. Previous studies demonstrated that circRNAs could act as miRNA sponges in cancer cells. In this study, we showed that knockdown of circCCDC66 induced expression of miR-211. Luciferase assay demonstrated that miR-211 suppressed the activity of luciferase reporter-contained circCCDC66 sequences. Moreover, knockdown of circCCDC66 significantly inhibited SRCIN1 levels in both A549 and H1299 cells. These results showed that circCCDC66 acted as a miRNA sponge to affect the miR-211/SRCIN1 axis. Of note, we for the first time revealed that circCCDC66 suppression reduced cell proliferation by about 65% in A549 and by about 40% in H1299 cells. We thought this study could provide novel potential biomarkers for NSCLC.
肺癌的发病率和死亡率极高。本研究表明 SRCIN1 是一种非小细胞肺癌（NSCLC）的癌基因。公共数据集分析表明，SRCIN1 在 NSCLC 样本中显著过表达。此外，我们通过分析 TCGA、Kaplan-Meier Plotter、GSE30219、GSE50081 和 GSE19188 数据库发现，SRCIN1 表达较高的 NSCLC 患者 OS 时间更短。过表达或敲低 SRCIN1 显著诱导或降低 A549 和 H1299 细胞的增殖。此外，我们发现 SRCIN1 被 miR-211 直接靶向。miR-211 的过表达或敲低抑制或诱导 NSCLC 中的 SRCIN1 水平。此外，我们发现 miR-211 通过 SRCIN1 影响 NSCLC 细胞的增殖。先前的研究表明，circRNAs 可以在癌细胞中作为 miRNA 的海绵。在这项研究中，我们表明 circCCDC66 的敲低诱导了 miR-211 的表达。荧光素酶报告基因实验表明，miR-211 抑制了含有 circCCDC66 序列的荧光素酶报告基因的活性。此外，circCCDC66 的敲低显著抑制了 A549 和 H1299 细胞中 SRCIN1 的水平。这些结果表明 circCCDC66 作为 miRNA 海绵影响 miR-211/SRCIN1 轴。值得注意的是，我们首次发现，circCCDC66 的抑制使 A549 细胞的增殖减少了约 65%，H1299 细胞的增殖减少了约 40%。我们认为这项研究为 NSCLC 提供了新的潜在生物标志物。
