HnRNP K regulates inflammatory gene expression by mediating splicing pattern of transcriptional factors

• Published in: Experimental biology and medicine (Maywood, N.J.) N.J.), 2023-09, Vol.248 (17), p.1479-1491
• Main Authors: Liu, Siyi, Duan, Yong, You, Ran, Chen, Dong, Tan, Jinhai
• Format: Article
• Language: English
• Subjects: Alternative Splicing - genetics; Gene Expression; HeLa Cells; Heterogeneous-Nuclear Ribonucleoprotein K - genetics; Heterogeneous-Nuclear Ribonucleoprotein K - metabolism; Humans; Transcription Factors - metabolism
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/15353702221110649

HnRNP K is a heterogeneous nuclear ribonucleoprotein and has been identified as an oncogene in most solid tumors via regulating gene expression or alternative splicing of genes by binding both DNA and pre-mRNA. However, how hnRNP K affects tumorigenesis and regulates the gene expression in cervical cancer (CESC) remains to be elucidated. In these data, higher expression of hnRNP K was observed in CESC and was negatively correlated with the patient survival time. We then overexpressed hnRNP K (hnRNP K-OE) and found that its overexpression promoted cell proliferation in HeLa cells (P = 0.0052). Next, global transcriptome sequencing (RNA-seq) experiments were conducted to explore gene expression and alternative splicing profiles regulated by hnRNP K. It is shown that upregulated genes by hnRNP K-OE were associated with inflammatory response and an apoptotic process of neuron cells, which involves in cancer. In addition, the alternative splicing of those genes regulated by hnRNP K-OE was associated with transcriptional regulation. Analysis of the binding features of dysregulated transcription factors (TFs) in the promoter region of the inflammatory response genes regulated by hnRNP K revealed that hnRNP K may modulate the expression level of genes related to inflammatory response by influencing the alternative splicing of TFs. Among these hnRNP K-TFs-inflammatory gene regulatory networks, quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments and gene silencing were conducted to verify the hnRNP K-IRF1-CCL5 axis. In conclusion, the hnRNP K-TFs-inflammatory gene regulatory axis provides a novel molecular mechanism for hnRNP K in promoting CESC and offers a new therapeutic target.