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In vitro evidence of NLRP3 inflammasome regulation by histone demethylase LSD2 in renal cancer: a pilot study

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Abstract

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.

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Acknowledgements

The authors are thankful to Indian Council of Medical Research, New Delhi, India for awarding junior and senior research fellowship (3/1/3/JRF-2013/HRD-071 (10440)). The authors would like to thank Professor Shobha Sehgal and Mr. Surya Prakash Sharma for their informative inputs throughout the study.

Funding

No funding was received for the study.

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Authors and Affiliations

  1. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Aman Kumar, Ujjawal Sharma, Niti Kumari & Rajendra Prasad

  2. Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Aman Kumar & Nayudu Nallabelli

  3. Department of Urology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Shrawan Kumar Singh

  4. Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Nandita Kakkar

Authors
  1. Aman Kumar
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  2. Nayudu Nallabelli
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  3. Ujjawal Sharma
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  4. Niti Kumari
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  5. Shrawan Kumar Singh
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  6. Nandita Kakkar
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  7. Rajendra Prasad
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Contributions

RP, SKS and NK directed the study. AK, NK and NN designed and performed experiments. AK, NK, NN, and US analysed and interpreted the data. AK, NN, and US wrote the manuscript.

Corresponding author

Correspondence to Rajendra Prasad.

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The authors declare no competing interests.

Ethical approval

The study was approved by Institute Ethics Committee (Ref No. NK/1597/Ph.D/10916). This study was conducted in accordance with the Declaration of Helsinki.

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Informed consent was taken from each participant before collecting the sample.

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Kumar, A., Nallabelli, N., Sharma, U. et al. In vitro evidence of NLRP3 inflammasome regulation by histone demethylase LSD2 in renal cancer: a pilot study. Mol Biol Rep 47, 7273–7276 (2020). https://doi.org/10.1007/s11033-020-05692-0

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  • DOI: https://doi.org/10.1007/s11033-020-05692-0

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