Overexpression of the mitochondrial anti-viral signaling protein, MAVS, in cancers is associated with cell survival and inflammation

Sweta Trishna; Avia Lavon; Anna Shteinfer-Kuzmine; Avis Dafa-Berger; Varda Shoshan-Barmatz

doi:10.1016/j.omtn.2023.07.008

Overexpression of the mitochondrial anti-viral signaling protein, MAVS, in cancers is associated with cell survival and inflammation

Mol Ther Nucleic Acids. 2023 Jul 17:33:713-732. doi: 10.1016/j.omtn.2023.07.008. eCollection 2023 Sep 12.

Authors

Sweta Trishna¹, Avia Lavon¹, Anna Shteinfer-Kuzmine², Avis Dafa-Berger¹, Varda Shoshan-Barmatz^{1

2}

Affiliations

¹ Department of Life Sciences, University of the Negev, Beer Sheva 84105, Israel.
² National Institute for Biotechnology in the Negev Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.

Abstract

Mitochondrial anti-viral signaling protein (MAVS) plays an important role in host defense against viral infection via coordinating the activation of NF-κB and interferon regulatory factors. The mitochondrial-bound form of MAVS is essential for its anti-viral innate immunity. Recently, tumor cells were proposed to mimic a viral infection by activating RNA-sensing pattern recognition receptors. Here, we demonstrate that MAVS is overexpressed in a panel of viral non-infected cancer cell lines and patient-derived tumors, including lung, liver, bladder, and cervical cancers, and we studied its role in cancer. Silencing MAVS expression reduced cell proliferation and the expression and nuclear translocation of proteins associated with transcriptional regulation, inflammation, and immunity. MAVS depletion reduced expression of the inflammasome components and inhibited its activation/assembly. Moreover, MAVS directly interacts with the mitochondrial protein VDAC1, decreasing its conductance, and we identified the VDAC1 binding site in MAVS. Our findings suggest that MAVS depletion, by reducing cancer cell proliferation and inflammation, represents a new target for cancer therapy.

Keywords: MAVS; MT: Non-coding RNAs; VISA; cancer; cell proliferation; inflammation; mitochondria; siRNA.