Department of Respiratory Medicine, The First People's Hospital of Nanning, No. 89 Qixing Road, Nanning, 530022, China.
J Cardiothorac Surg. 2022 Mar 21;17(1):46. doi: 10.1186/s13019-022-01788-9.
The morbidity of lung cancer ranks first among all cancers. Lung adenocarcinoma (LUAD) is a classification of lung cancer, and cell invasion and migration of LUAD are the main causes for its high mortality. Therefore, further exploring the potential mechanism of LUAD metastasis may provide bases for following targeted drug development and treatment of LUAD. In this study, clinical data as well as gene expression profiles were obtained from TCGA-LUAD and GEO to analyze CTHRC1 expression. The result found that CTHRC1 was significantly high in LUAD. Similar results were also discovered in 4 cancer cell lines. Moreover, overexpressed/knock-down CTHRC1 cell lines were constructed. It was uncovered that overexpressing CTHRC1 promoted LUAD cell migration and invasion, and inhibited cell adhesion, while knocked down CTHRC1 had the opposite effect. Afterward, the upstream miRNAs that regulated CTHRC1 were predicted by several bioinformatics websites. It was testified by dual-luciferase method that CTHRC1 was negatively mediated by miR-30a-5p. Overexpressed miR-30a-5p suppressed cell invasion/migration, and increased cell adhesion, while overexpressing CTHRC1 as well reversed such impacts. In conclusion, it was disclosed in this study that CTHRC1 worked as a cancer promoter in LUAD, and miR-30a-5p could target and downregulate CTHRC1 to regulate cell adhesion, and inhibited LUAD cell invasion and migration. These results elucidated at cellular level that upregulated CTHRC1 may be a marker protein for LUAD metastasis.
肺癌的发病率在所有癌症中位居第一。肺腺癌（LUAD）是肺癌的一种分类，LUAD 的细胞侵袭和迁移是其高死亡率的主要原因。因此，进一步探索 LUAD 转移的潜在机制可能为后续靶向药物开发和 LUAD 治疗提供依据。本研究从 TCGA-LUAD 和 GEO 中获取临床数据和基因表达谱，分析 CTHRC1 的表达。结果发现 LUAD 中 CTHRC1 显著升高。在 4 种癌细胞系中也发现了相似的结果。此外，构建了过表达/敲低 CTHRC1 的细胞系。结果表明，过表达 CTHRC1 促进 LUAD 细胞迁移和侵袭，抑制细胞黏附，而敲低 CTHRC1 则产生相反的效果。随后，通过几个生物信息学网站预测调节 CTHRC1 的上游 miRNA。双荧光素酶实验证实 CTHRC1 受 miR-30a-5p 的负调控。过表达 miR-30a-5p 抑制细胞侵袭/迁移，增加细胞黏附，而过表达 CTHRC1 则逆转了这种影响。综上所述，本研究揭示了 CTHRC1 在 LUAD 中作为癌基因发挥作用，miR-30a-5p 可以靶向并下调 CTHRC1 来调节细胞黏附，并抑制 LUAD 细胞侵袭和迁移。这些结果从细胞水平阐明了上调的 CTHRC1 可能是 LUAD 转移的标记蛋白。
