Department of Medical Oncology, Xuzhou Central Hospital, XuZhou 221009, China.
Department of Urinary Surgery, Xuzhou Central Hospital, XuZhou 221009, China.
Biochem Biophys Res Commun. 2018 Jun 12;500(4):846-851. doi: 10.1016/j.bbrc.2018.04.172. Epub 2018 Apr 26.
Lung cancer characterized with malignant cell growth is the leading cause of cancer-related deaths. In recent years, several circular RNAs (circRNAs) have been reported to participate in lung cancer progression. However, the correlation between circular RNA (circRNA) and lung cancer still remains to be further investigated. In this study, we screened out a highly expressed circular RNA hsa_circRNA_103809 in lung cancer tissues. We showed hsa_circRNA_103809 could serve as a prognostic biomarker for patients with lung cancer. Furthermore, we found that hsa_circRNA_103809 knockdown significantly suppressed lung cancer cell proliferation and invasion in vitro and delayed tumor growth in vivo. In mechanism, we identified hsa_circRNA_103809 as a sponge of miR-4302 targeting ZNF121. By sequestering miR-4302, hsa_circRNA_103809 promoted the expression of ZNF121 which consequently enhanced MYC protein level in lung cancer cells. Through rescue assays, we demonstrated hsa_circRNA_103809 contributed to lung cancer cell proliferation and invasion via facilitating ZNF121-dependent MYC expression by sponging miR-4302. In conclusion, our findings illustrated a novel hsa_circRNA_103809/miR-4302/ZNF121/MYC regulatory signaling pathway in lung cancer progression.
肺癌的特征是恶性细胞生长，是癌症相关死亡的主要原因。近年来，有报道称几种环状 RNA（circRNA）参与肺癌的进展。然而，circRNA 与肺癌之间的相关性仍有待进一步研究。在本研究中，我们筛选出肺癌组织中高度表达的环状 RNA hsa_circRNA_103809。我们表明 hsa_circRNA_103809 可以作为肺癌患者的预后生物标志物。此外，我们发现 hsa_circRNA_103809 敲低显著抑制了肺癌细胞在体外的增殖和侵袭，并延迟了体内肿瘤的生长。在机制上，我们鉴定出 hsa_circRNA_103809 是 miR-4302 靶向 ZNF121 的海绵。通过隔离 miR-4302，hsa_circRNA_103809 促进了 ZNF121 的表达，从而增强了肺癌细胞中 MYC 蛋白水平。通过挽救实验，我们证明 hsa_circRNA_103809 通过海绵 miR-4302 促进 ZNF121 依赖性 MYC 表达，从而促进肺癌细胞的增殖和侵袭。总之，我们的研究结果说明了一个新的 hsa_circRNA_103809/miR-4302/ZNF121/MYC 调控信号通路在肺癌进展中的作用。
