Investigation of the possible oncogenic role of NLRP7 in human endometrium canser

Abstract

NLRP7 is an innate immune protein that is involved in the activation of proin ammatory caspases by participating in in ammasome oligomerization. So far, mutations in NLRP7 have been associated with Hydatidiform Mole disease, characterized by excessive trophoblastic proliferation and lack of embryo development. Besides, NLRP7 is proposed to have an oncogenic role since its expression levels signi cantly increase in testicular seminoma and endometrial cancer tissues. However, the mechanism( s) behind its oncogenic contribution is currently unknown. Here, we analyzed the protein interactome of NLRP7 to fully elucidate putative pathways and molecular mechanisms through which NLRP7 may drive oncogenesis in the context of human endometrium cancer. We conducted protein network analysis using the Ingenuity Pathway tool, which showed that the Ras pathway is at the center of the network comprised by NLRP7 interactors. Then, we validated the physical interaction between NLRP7 and selected partners using co-immunoprecipitation. Our initial results indicated that NLRP7 might be an e ector protein of two Ras-related GTPases and it also may interfere with the DNA damage response pathways via ATM-Brat1-Chk1 axis. Moreover, we showed that NLRP7 is modi ed by Small Ubiquitin-Like Modi er (SUMO), which may explain its upregulation in human endometrium cancer. Taken together, our results illuminate a protein network of NLRP7, show novel interaction partners and a modi cation of the same protein, and provide new insights into the contribution of NLRP7 to oncogenesis. We expect that our results will lead to a better understanding of the role of NLRP7 in human endometrium cancer and possibly pave the way for future therapies.