Differential expression of NF-κB heterodimer RelA/p50 in human urothelial carcinoma

Abstract

BackgroundUrothelial carcinoma (UC) is the fifth most common malignancy that accounts for 5% of all cancers. Diagnostic markers that predict UC progressions are inadequate. NF-κB contributes towards disease progression upon constitutive activation in many solid tumors. The nuclear localization of NF-κB indicates increased transcriptional activity while cytoplasmic localization indicates the inactive protein repository that can be utilized readily by a malignant cell. This study delineates the nuclear and cytoplasmic differential expression of NF-κB heterodimers in UC progression.MethodsThe involvement of the NF-κB proteins in UC was analyzed in silico using cytoscape. The expression of NF-κB heterodimers was analyzed by immunohistochemistry.ResultsPINA4MS app in cytoscape revealed over expression of RelA and suppression of NF-κB1 (p50 precursor) in UC whereas the expression of NF-κB target proteins remained unhindered. Immunohistochemical localization showed nuclear RelA/p50 in low grade UC whereas in high grade only RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50 remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear and cytoplasmic expression (p < 0.005) was directly proportional to the disease progression. In our study, some of the high-grade UC tissues with squamous differentiation and muscle invasion had extensive nuclear p50 localization. The phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade UC might be due to their interaction with other members of NF-κB family of proteins. Thus, NF-κB RelA/p50 differential expression may play a unique role in UC pathogenesis and can serve as a biomarker for diagnosis.

Circular RNA profiling reveals a potential role of hsa_circ_IPCEF1 in papillary thyroid carcinoma

“…In cancer cells, chronic activation and nuclear localization result in NF-κB1 accumulation and NF-κB activation, which stimulate cell survival by inducing anti-apoptotic gene expression (61). Recently, NF-κB1 has been proved to be upregulated in a variety of cancers, including subungual keratoacanthoma, urothelial carcinoma and breast cancer, suggesting that it is a biomarker for diagnosis and treatment (62)(63)(64)(65)(66). In the results of the present study, NF-κB1 was predicted to be a ceRNA of hsa_circ_IPCEF1 regulation and the downregulation of hsa_circ_IPCEF1 in PTC was accompanied by the upregulation of NF-κB1, suggesting that a combination of hsa_circ_IPCEF1 and NF-κB1 could be used as biomarkers for PTC diagnosis/prognosis.…”

Selective Susceptibility of Human Bladder Transitional Cell Carcinoma T24 Cells towards NBD Peptide

“…Targeted therapy is sought after in the treatment of BC (Jones et al, 2016) overexpression of NF-κB heterodimers can be used to differentiate cancer cells from normal cells. Previously, we were able to show that the NF-κB RelA preferably binds to other dimers of the family other than p50 during BC progression (Durairajan et al, 2018). Since the involvement of the NF-κB heterodimers in BC progression was evident, we utilized this to explore the treatment potential by targeting this pathway.…”

“…Proteosome inhibitors are the only exception from this trait which is used for the treatment of some haematological malignancies that demonstrate the key role of NF-κB during their pathogenesis (Richardson et al, 2004). There are many reports stating the involvement of NF-κB in BC (Durairajan et al, 2018;Levidou et al, 2008;Mukherjee et al, 2015;Yeh et al, 2010). However, there are limited reports that have considered the NF-κB signaling cascade and BC in a therapeutic setting.…”