Abstract
Our previous studies showed that Fibroblast growth factor receptor 3 (FGFR3) contributed to cell growth in lung cancer. However, the correlation between FGFR3 and tumor progression, coupled with the underlying mechanisms, are not fully understood. The clinical significance of FGFR3 was determined in two cohorts of clinical samples (n = 22, n = 78). A panel of biochemical assays and functional experiments was utilized to elucidate the underlying mechanisms and effects of FGFR3 and miR-24-3p on lung adenocarcinoma progression. Upregulated FGFR3 expression indicated an adverse prognosis for lung adenocarcinoma individuals and promoted metastatic potential of lung adenocarcinoma cells. Owing to the direct regulation towards FGFR3, miR-24-3p could interfere with the potential of proliferation, migration, and invasion in lung adenocarcinoma, following variations of EMT-related protein expression. As a significant marker of EMT, E-cadherin was negatively correlated with FGFR3, of which ectopic overexpression could neutralize the antitumour effects of miR-24-3p and reverse its regulatory effects on EMT markers. Taken together, these findings define a novel insight into the miR-24-3p/FGFR3 signaling axis in regulating lung adenocarcinoma progression and suggest that targeting the miR-24-3p/FGFR3 axis could be an effective and efficient way to prevent tumor progression.
Highlights
As its lethality rate ranks near the top, lung cancer is regarded as a very common malignancy [1]
Fibroblast growth factor receptor 3 (FGFR3) protein was dramatically decreased in these cells with indicated treatments (Figure 2(d), second panel). These results demonstrated that the FGFR3 protein instead of FGFR3 mRNA was downregulated by miR-24-3p in lung adenocarcinoma cells, further indicating that the regulation of FGFR3 was based on miR-24-3p-mediated posttranscriptional modification
In accordance with our previous study, where FGFR3 was regarded as an oncogene that promoted lung cancer cell growth [8], we revealed a novel metastasis mechanism of lung adenocarcinoma by that FGFR3 was negatively affected by miR-24-3p and possessed a negative correlation with E-cadherin protein, enabling cancer cell metastasis by the regulation of epithelial-mesenchymal transition (EMT)-related proteins
Summary
As its lethality rate ranks near the top, lung cancer is regarded as a very common malignancy [1]. More than 90% of cancerrelated deaths in nonsmall cell lung cancer (NSCLC) are triggered by tumor progression, especially metastasis [1, 2]. Being a primary subtype of NSCLC, lung adenocarcinoma is liable to metastasize at early stage than lung squamous carcinoma. It is necessary to investigate the mechanisms related to lung adenocarcinoma metastasis. Overexpression or activation of some oncogenes could draw a dramatic shift in cancer cell performance, such as improving proliferative or metastatic potentials of tumor cells. Fibroblast growth factor receptors (FGFRs) mediate a set of development-related pathways, such as the formation of mesoderm during the early embryonic stage and the development of multiple organs and systems.
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