HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells

基于生物信息学分析的预后和免疫治疗反应预测因子HNRNPC与NSCLC细胞增殖和侵袭有关

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作者:Zhuoyu Gu #, Yang Yang #, Qian Ma #, Hui Wang, Song Zhao, Yu Qi, Yixin Li

Background

Little is known about the relationship between N6-methyladenosine (m6A)-related genes and tumor immune microenvironment (TIME) in non-small cell lung cancer (NSCLC). It is unclear which m6A regulators are essential for NSCLC progression. The

Conclusions

M6A regulator HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells.

Methods

Based on bioinformatics analysis, heterogeneous nuclear ribonucleoprotein C (HNRNPC) was considered as the most influential m6A regulator. Further study was investigated using patient samples, stable cell lines, and xenograft mice models.

Results

The differentially expressed profiles of m6A-related genes were established in NSCLC, and the NSCLC samples were clustered into two subtypes with different immune infiltration and survival time. Next, we found that the risk score (RS) based on m6A-related genes was a predictor of prognosis and immunotherapy response for NSCLC, in which HNRNPC was considered as the most influential m6A regulator. In NSCLC patients, we confirmed that HNRNPC predicted poor prognosis and correlated with tumor invasion and lymph node metastasis. RNA-seq data revealed that HNRNPC was involved in cell growth, cell migration, extracellular matrix organization and angiogenesis. In vitro, we verified that HNRNPC knockdown attenuated the cell proliferation, clonogenicity, invasion and migration. In vivo, HNRNPC knockdown inhibited the tumor growth and lung metastasis. Additionally, HNRNPC knockdown was associated with high CD8 + T cell infiltration, along with elevated CD4 + T cell infiltration, collagen production and angiogenesis. Conclusions: M6A regulator HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells.

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