Aoyang Institute of Cancer, Jiangsu University, Suzhou, China.
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.
Cell Cycle. 2021 Mar-Mar;20(5-6):522-536. doi: 10.1080/15384101.2021.1878327. Epub 2021 Jan 27.
Circular RNAs (circRNAs) are considered as a new regulatory factor in growth, metastasis and therapeutic resistance of human cancers. But the clinical significance and underlying mechanism of circular RNA ITCH (circ-ITCH) in gastric cancer (GC) remain unknown. In the present study, we found that circ-ITCH was down-regulated in GC cell lines, GC tissues and their serum-derived exosomes. The level of circ-ITCH was related to invasion depth. Functional assays showed that circ-ITCH overexpression inhibited the proliferation, migration, invasion and epithelial mesenchymal transition (EMT) of GC cells, whereas circ-ITCH knockdown appeared an opposite effect. Bioinformatic analysis and luciferase reporter assay confirmed that circ-ITCH acted as miR-199a-5p sponge and increased the level of Klotho. The expression level of miR-199-5p was up-regulated in GC tissues and negatively correlated with that of circ-ITCH. MiR-199a-5p mimics reversed the effects on inhibiting metastasis induced by circ-ITCH overexpression and decreased the level of Klotho in GC cells. Our findings indicate that circ-ITCH suppresses metastasis of GC by acting as the sponge of miR-199a-5p and increasing Klotho expression, which serves as a potential biomarker and targets for the diagnosis and therapy of GC. CircRNAs: circular RNAs; GC: gastric cancer; circ-ITCH: circular RNA Itchy E3 ubiquitin protein ligase; ceRNA: competitive endogenous RNA; EMT: Epithelial-mesenchymal transition; siRNA: Small interfering RNA; TEM: transmission electron microscope; NTA: nanoparticle tracking analysis.
环状 RNA（circRNAs）被认为是人类癌症生长、转移和治疗耐药性的新调节因子。但是环状 RNAITCH（circ-ITCH）在胃癌（GC）中的临床意义和潜在机制尚不清楚。在本研究中，我们发现 circ-ITCH 在 GC 细胞系、GC 组织及其血清衍生的外泌体中表达下调。circ-ITCH 的水平与浸润深度有关。功能分析表明，circ-ITCH 过表达抑制 GC 细胞的增殖、迁移、侵袭和上皮间质转化（EMT），而 circ-ITCH 敲低则出现相反的效果。生物信息学分析和荧光素酶报告基因实验证实 circ-ITCH 作为 miR-199a-5p 的海绵体，增加了 Klotho 的水平。miR-199a-5p 在 GC 组织中的表达上调，并与 circ-ITCH 的表达呈负相关。miR-199a-5p 模拟物逆转了 circ-ITCH 过表达抑制转移的作用，并降低了 GC 细胞中 Klotho 的水平。我们的研究结果表明，circ-ITCH 通过作为 miR-199a-5p 的海绵体和增加 Klotho 表达来抑制 GC 的转移，这可作为 GC 诊断和治疗的潜在生物标志物和靶点。
