The study aimed to explore the functional role of fibronectin type III domain containing 1 (FNDC1) in nonsmall cell lung cancer (NSCLC), as well as the mechanism governing its expression. The expression levels of FNDC1 and related genes in tissue and cell samples were detected by qRT-PCR. Kaplan-Meier analysis was employed to analyze the association between FNDC1 level and the overall survival of NSCLC patients. Functional experiments such as CCK-8 proliferation, colony formation, EDU staining, migration and invasion assays were conducted to investigate the functional role of FNDC1 in regulating the malignancy of NSCLC cells. Bioinformatic tools and dual-luciferase reporter assay were used to identify the miRNA regulator of FNDC1 in NSCLC cells. Our data revealed the upregulation of FNDC1 at mRNA and protein levels in NSCLC tumor tissues cancer cell lines, compared with normal counterparts. NSCLC patients with higher FNDC1 expression suffered from a poorer overall survival. FNDC1 knockdown significantly suppressed the proliferation, migration and invasion of NSCLC cells, and had an inhibitory effect on tube formation. We further demonstrated that miR-143-3p was an upstream regulator of FNDC1 and miR-143-3p expression was repressed in NSCLC samples. Similar to FNDC1 knockdown, miR-143-3p overexpression inhibited the growth, migration and invasion of NSCLC cells. FNDC1 overexpression could partially rescue the effect of miR-143-3p overexpression. FNDC1 silencing also suppressed the tumorigenesis of NSCLC cells in mouse model. In conclusion, FNDC1 promotes the malignant prototypes of NSCLC cells. miR-143-3p is a negative regulator of FNDC1 in NSCLC cells, which may serve as a promising therapeutic target in NSCLC.

中文翻译：

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miR-143-3p/FNDC1轴在非小细胞肺癌进展中的作用。

该研究旨在探讨纤连蛋白III型结构域1（FNDC1）在非小细胞肺癌（NSCLC）中的功能作用及其表达的机制。采用qRT-PCR检测组织和细胞样本中FNDC1及相关基因的表达水平。采用Kaplan-Meier分析来分析FNDC1水平与NSCLC患者总生存期之间的关联。通过CCK-8增殖、集落形成、EDU染色、迁移和侵袭实验等功能实验来研究FNDC1在调节NSCLC细胞恶性中的功能作用。使用生物信息学工具和双荧光素酶报告基因测定来鉴定 NSCLC 细胞中 FNDC1 的 miRNA 调节因子。我们的数据显示，与正常细胞相比，NSCLC 肿瘤组织癌细胞系中 FNDC1 的 mRNA 和蛋白质水平上调。FNDC1 表达较高的 NSCLC 患者的总生存期较差。FNDC1敲低显着抑制NSCLC细胞的增殖、迁移和侵袭，并对管形成有抑制作用。我们进一步证明 miR-143-3p 是 FNDC1 的上游调节因子，并且 miR-143-3p 表达在 NSCLC 样本中受到抑制。与 FNDC1 敲低类似，miR-143-3p 过表达抑制 NSCLC 细胞的生长、迁移和侵袭。FNDC1 过表达可以部分挽救 miR-143-3p 过表达的影响。FNDC1 沉默还抑制了小鼠模型中 NSCLC 细胞的肿瘤发生。总之，FNDC1 促进 NSCLC 细胞的恶性原型。miR-143-3p 是 NSCLC 细胞中 FNDC1 的负调节因子，可能作为 NSCLC 的一个有前途的治疗靶点。