RBM14 as a novel epigenetic-activated tumor oncogene is implicated in the reprogramming of glycolysis in lung cancer

RBM14 作为一种新的表观遗传激活肿瘤致癌基因,与肺癌糖酵解重编程有关

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作者:Yan Hu, Hanshuo Mu, Zhiping Deng

Background

RNA-binding motif protein 14 (RBM14) is upregulated in a variety of tumors. However, the expression and biological role of RBM14 in lung cancer remain unclear.

Conclusions

These results indicated that epigenetically activated RBM14 regulated growth and apoptosis by regulating the reprogramming of glycolysis and RBM14 may serve as a promising biomarker and therapeutic target for LUAD.

Methods

Chromatin immunoprecipitation and PCR were carried out to measure the levels of sedimentary YY1, EP300, H3K9ac, and H3K27ac in the RBM14 promoter. Co-immunoprecipitation was used to verify the interaction between YY1 and EP300. Glycolysis was investigated according to glucose consumption, lactate production, and the extracellular acidification rate (ECAR).

Results

RBM14 level is increased in lung adenocarcinoma (LUAD) cells. The increased RBM14 expression was correlated with TP53 mutation and individual cancer stages. A high level of RBM14 predicted a poorer overall survival of LUAD patients. The upregulated RBM14 in LUAD is induced by DNA methylation and histone acetylation. The transcription factor YY1 directly binds to EP300 and recruits EP300 to the promoter regions of RBM14, which further enhances H3K27 acetylation and promotes RBM14 expression. YY1-induced upregulation of RBM14 promoted cell growth and inhibited apoptosis by affecting the reprogramming of glycolysis. Conclusions: These results indicated that epigenetically activated RBM14 regulated growth and apoptosis by regulating the reprogramming of glycolysis and RBM14 may serve as a promising biomarker and therapeutic target for LUAD.

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