NLRP3 pathway plays a vital role in the pathogenesis of different human cancers but still the regulation of NLRP3 pathway largely unknown. Therefore, we examined the levels of NLRP3 and its downstream components (caspase-1 and IL-1β) and its relationship with histone modifiers in renal cancer pathogenesis. Total 30 cases of clear cell renal cell carcinoma (ccRCC), were studied for NLRP3, caspase-1 and IL-1β expression using real-time PCR, which showed the augmented levels of all the three components of NLRP3 inflammasome pathway in ccRCC. Next, role of the FAD dependent monoamine oxidases (LSD2) and jumonji C (JmjC)-domain-containing, iron-dependent dioxygenases (KDM5A) histone demethylases were evaluated in regulation of NLRP3 inflammasome pathway in-vitro using RCC cell line. It was observed that silencing of KDM5A didn't alter the levels of neither of the NLRP3 component but inhibition of LSD2 showed significant effect on NLRP3 expression while no change in caspase-1 and IL-1β levels. This study suggests that rather LSD2 not KDM5A lysine demethylase family might be involved in the regulation of NLRP3 inflammasome in cancer cells which could be useful for deciphering the future therapeutic targets for the disease.
Molecular biology reports. 2020 Aug 04 [Epub ahead of print]
Aman Kumar, Nayudu Nallabelli, Ujjawal Sharma, Niti Kumari, Shrawan Kumar Singh, Nandita Kakkar, Rajendra Prasad
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India., Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India. .