RNA Helicase p68 Deploys β-Catenin in Regulating RelA/P65 Gene Expression

RelA/p65 is a crucial member of NF-κB signaling pathway. Limited knowledge prevails on the mechanistic insights of RelA gene regulation. RNA helicase p68 acts as a &nbsp;transcriptional coactivator of several oncogenic transcription factors. Here we report, a &nbsp;novel mechanism of alliance between p68 and β-catenin in regulating the expression of &nbsp;RelA. p68, β-catenin and RelA proteins were found to bear strong positive correlation &nbsp;in normal and colon carcinoma patient samples. Both p68 and β-catenin increased &nbsp;RelA mRNA and protein expression. p68 and Wnt3a elevated RelA promoter activity&nbsp;and p68 was perceived to occupy RelA promoter with β-catenin at the TCF4/LEF (TBE) sites. p68 and β-catenin alliance positively modulated the expression of signature NF-βB target genes. Enhanced NF-βB target gene expression by p68 was corroborated by &nbsp;findings in clinical samples and mice colorectal allograft models. This study unravels &nbsp;novel modes of p68-mediated oncogenesis, marking it a potential target for therapy.<br><br>Funding: This work is supported by grants received from DST {Nano Mission programme (SR/NM/NS-1058/2015), SERB (EMR/2017/001183)} and CSIR, Govt. of India to Dr. Mrinal K Ghosh.<br><br>Declaration of Interest: The authors declare no competing interests.<br><br>Ethical Approval: All clinical and ethical regulations were followed for collecting the samples, including patient consent and with formal approval from the ethical committee of both CSIR-IICB and Park Clinic. All animal care and experimentation were conducted according to the CPCSEA guidelines; with approval of the animal ethics committee at CSIR-Indian Institute of Chemical Biology.