Background: The incidence rate and mortality rate of lung cancer are the highest in the world. Therefore, further studies are needed to reveal the molecular mechanism of lung cancer progression and development. Previous study demonstrated that the deregulation of circRNAs can regulate cell biological functions in tumorigenesis and development. However, the roles of circPTCH1 in lung cancer have not yet been revealed.
Materials and Methods: The expression levels of circPTCH1, miR-34c-5p, and MYCN were measured by RT-PCR in lung cancer tissues and cells; dual-luciferase reporter and RIP assay showed that circRNA served as a sponge for miRNA, and miRNA could target mRNA. In vitro, effects of si-circPTCH1 can regulate lung cancer cells’ migration, invasion were detected by CCK-8 assay, wound healing assay, and transwell assay.
Results: Our research demonstrated that the expression of circPTCH1 was upregulated in lung cancer tissues and cell lines and increased in metastatic tissues compared to that of non-metastatic tissues. circPTCH1 sponging miR-34c-5p to target MYCN was revealed by dual-luciferase reporter and a RIP assay. In addition, the expression level of miR-34c-5p was reduced in lung cancer tumor tissues, and MYCN was significantly increased in lung cancer tumor tissues. Pearson correlation analysis showed that miR-34c-5p with circPTCH1 and MYCN had a moderately negative correlation, and there was a moderately positive correlation between circPTCH1 and MYCN. Further, cytological studies found that circPTCH1 reduced lung cancer cells’ migration and invasion by targeting MYCN via miR-34c-5p.
Conclusion: circPTCH1 plays a tumor enhancement role in lung cancer and that can effectively promote migration, invasion and EMT by targeting the miR-34c-5p/MYCN axis. circPTCH1 may be a novel potential treatment and diagnosis biomarker for lung cancer.



中文翻译：

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CircPTCH1 通过 miR-34c-5p 调节 MYCN 表达促进肺癌迁移


背景：肺癌的发病率和死亡率是世界上最高的。因此，需要进一步研究揭示肺癌进展和发展的分子机制。先前的研究表明，circRNA的失调可以调节肿瘤发生和发展中的细胞生物学功能。然而，circPTCH1在肺癌中的作用尚未被揭示。

材料与方法：采用RT-PCR法检测肺癌组织和细胞中circPTCH1、miR-34c-5p、MYCN的表达水平；双荧光素酶报告基因和RIP检测表明，circRNA充当miRNA的海绵，并且miRNA可以靶向mRNA。在体外，通过CCK-8实验、伤口愈合实验和Transwell实验检测si-circPTCH1可以调节肺癌细胞的迁移、侵袭。

结果：我们的研究表明，与非转移组织相比，circPTCH1在肺癌组织和细胞系中表达上调，在转移组织中表达增加。双荧光素酶报告基因和 RIP 测定揭示了 circPTCH1 海绵 miR-34c-5p 靶向 MYCN。此外,肺癌肿瘤组织中miR-34c-5p表达量降低,肺癌肿瘤组织中MYCN表达量显着升高。 Pearson相关分析显示，miR-34c-5p与circPTCH1、MYCN呈中度负相关，circPTCH1与MYCN呈中度正相关。此外，细胞学研究发现，circPTCH1通过miR-34c-5p靶向MYCN，从而减少肺癌细胞的迁移和侵袭。

结论： circPTCH1在肺癌中发挥肿瘤增强作用，可通过靶向miR-34c-5p/MYCN轴有效促进迁移、侵袭和EMT。 circPTCH1可能是一种新型潜在的肺癌治疗和诊断生物标志物。