TCF19 promotes cell proliferation and tumor formation in lung cancer by activating the Raf/MEK/ERK signaling pathway

Abstract

Objective This study aimed to investigate the role of TCF19 in lung cancer, focusing on its impact on the development and progression of tumors. Specifically, the objective was to elucidate the molecular mechanisms underlying TCF19-mediated effects, with a particular emphasis on its involvement in the RAF/MEK/ERK signaling pathway. Methods The research involved the analysis of lung cancer tissues to assess the expression levels of TCF19. In vitro experiments were conducted using lung cancer cells (A549 and Hop62) with TCF19 overexpression. Transgenic mouse models were employed to study the in vivo effects of TCF19 on the development of primary tumors. Transcriptome sequencing was performed to identify alterations in gene expression profiles, and further experiments were carried out to investigate the activation status of the RAF/MEK/ERK pathway. Functional assays, including cell cycle progression and the levels of cell cycle-associated proteins, were conducted to understand the underlying mechanisms. Results The research findings demonstrated significant overexpression of TCF19 in lung cancer tissues. In vitro experiments revealed that TCF19 overexpression stimulated the growth of lung cancer cells and facilitated the development of primary tumors in transgenic mice. Mechanistically, TCF19 overexpression was associated with an elevation in the Ras and MAPK signaling pathways, as indicated by increased phosphorylation of Raf1, MEK1/2, and ERK1/2 in A549 and Hop62 cells. However, the inhibition of RAF1 or ERK, either through shRaf1 or ERK inhibitor, led to a reduction in cell cycle-related proteins and inhibited cell growth in TCF19-overexpressing cells. Conclusion In conclusion, this study identified TCF19 as an oncogene in lung carcinoma. The research highlighted its specific impact on the RAF/MEK/ERK signaling pathway, offering insights into a novel aspect of the molecular cascade involved in lung cancer development. Targeting TCF19 or its associated signaling pathways may present a promising avenue for the management of lung cancer characterized by elevated TCF19 levels.