Background RelA/p65 a crucial member of NF-κB signaling pathway plays diverse role in mediating oncogenesis. Limited knowledge prevails on the mechanistic insights of RelA gene regulation. RNA helicase p68 apart from being a vital player of RNA metabolism acts as a transcriptional coactivator of several oncogenic transcription factors including β-catenin and is highly implicated in cancer progression. In this study, we aim to discern the molecular mechanism of how an RNA helicase, p68 deploys a major oncogenic signaling pathway, Wnt/ β-catenin to regulate the expression of RelA, an indispensable component of NF-κB signaling pathway towards driving colon carcinogenesis. Methods Immunoblotting and quantitative RT-PCR was performed for determining the protein and mRNA expressions of the concerned genes respectively. Luciferase assay was employed for studying the promoter activity of RelA. Chromatin immunoprecipitation was used to evaluate the occupancy of transcription factors on the RelA promoter. Immunohistochemical analysis was conducted using FFPE sections derived from normal human colon and colon cancer patient samples. Finally, a syngeneic colorectal allograft mouse model was used to assess physiological significance of the in vitro findings. Results p68, β-catenin and RelA proteins were found to bear strong positive correlation in normal and colon carcinoma patient samples. Both p68 and β-catenin increased RelA mRNA and protein expression. p68, β-catenin and Wnt3a elevated RelA promoter activity. Conversely, p68 and β-catenin knockdown diminished RelA promoter activity and led to reduced RelA mRNA and protein expression. p68 was perceived to occupy RelA promoter with β-catenin at the TCF4/LEF (TBE) sites thereby potentiating RelA transcription. p68 and β-catenin alliance positively modulated the expression of signature NF-κB target genes. Enhanced NF-κB target gene expression by p68 was corroborated by findings in clinical samples. Tumors generated in mice colorectal allograft model, stably expressing p68 further reinforced our in vitro findings. Conclusions We report for the first time a novel mechanism of alliance between p68 and β-catenin in regulating the expression of RelA and stimulating the NF-κB signaling axis towards driving colon carcinogenesis. This study unravels novel modes of p68-mediated colon carcinogenesis, marking it a potential target for therapy. Electronic supplementary material The online version of this article (10.1186/s13046-019-1304-y) contains supplementary material, which is available to authorized users.

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Context: Oral Lichen planus (OLP) is a chronic, debilitating, immune-mediated disease whose management is considered a challenge in medical science. Aims: To quantitatively evaluate the effect of administration of enteral hydroxychloroquine (HCQS) as a monotherapy for six months on the extent and severity of erosive OLP using reticular score, erythema score and ulcerative score (REU score), and to subjectively evaluate the success of HCQS as a therapeutic drug for OLP-e using Tel Aviv-San Francisco Scale, visual analogue scale (VAS) and severity of burning sensation (BURN score). Settings and Design: Prospective clinical trial. Methods and Material: A total of 45 subjects received 200 mg of HCQS bid for six months. REU, VAS, BURN scores and Tel Aviv-San Francisco Scale readings were taken at the beginning of the study (baseline) and three- and six-month intervals post administration of enteral HCQS. Subjects were examined for any adverse drug outcomes for one year after the cessation of enteric HCQS therapy. Data were analysed with SPSS version 25. Results: There was a stark reduction in REU, VAS and BURN scores during the study period, with a statistically significant reduction (P < 0.05) seen at three- and six-month time intervals as compared to baseline. Further, the mean of change in R, E and U scores showed a statistically significant difference, with the highest reduction seen at baseline to six-month time interval. The Tel Aviv-San Francisco Scale showed 70%–100% remission in disease in more than 70% of subjects. Conclusions: Enteral HCQS can be considered a viable treatment option for the enigma that is erosive OLP.