Biology subjects

Eleya, S.

Publications and source records attributed to Eleya, S..

4 recordsLinked to original sources

bioRxiv2026

Targeting NAT10 Activates Tumor-Intrinsic Immunity and Suppresses Tumor Progression in Head and Neck Squamos Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) remain a major clinical challenge due to its high heterogeneity and limited therapeutic response, resulting in a 5-year overall survival rate of only [~]50%. Identifying molecular pathways that drive tumor progression while suppressing anti-tumor immunity is therefore critical for developing more effective therapies. N-acetyltransferase 10 (NAT10) is the only known enzyme responsible for catalyzing the RNA modification N4-acetylcytidine (ac4C) on rRNA, tRNA, and mRNA, and has been implicated in tumor progression in several cancers. In this study, we identify NAT10 as a key suppressor of tumor-intrinsic immune signaling in HNSCC. NAT10 expression was significantly elevated in tumor tissues and HNSCC cell lines and was associated with poor overall survival. Moreover, high-risk HPV, a major etiological factor in HNSCC, upregulated NAT10 protein expression through the viral oncoproteins E6 and E7. Functional inhibition of NAT10, either by genetic depletion or the small-molecule inhibitor Remodelin, activated tumor-intrinsic innate immune responses, as evidenced by increased IRF3 phosphorylation and induction of type I/II interferons and interferon-stimulated genes. Depletion of NAT10 was able to suppress tumorigenic phenotypes, including cell proliferation, migration, and colony formation in HNSCC cells. Importantly, activation of the STING signaling pathway using agonist cyclic di-GMP further amplified immune activation in NAT10-inhibited cancer cells. Together, our findings establish NAT10 as a previously unrecognized negative regulator of tumor-intrinsic immunity in HNSCC and support NAT10 targeting, particularly in combination with STING agonists, as a promising immunotherapeutic strategy.

Cancer Biology↗

bioRxiv2026

Levosimendan inhibits HIV-1 infection in myeloid cells in the RIOK1-dependent manner

Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, including circulating monocytes and tissue-resident macrophages, and integrates with host genomes to form stable viral reservoirs. To achieve a functional HIV cure, latency-promoting agents (LPAs) have been developed for the "block-and-lock" strategy to reinforce deep HIV-1 latency and permanently silence proviruses. However, most LPAs have been tested mainly in CD4+ T cells, and their efficacy in myeloid cells remains unclear. In this study, we reported that levosimendan (LSM), a drug approved for clinic use to treat heart failures, is able to inhibit HIV lytic infection and reactivation in myeloid cells. LSM blocked viral lytic reactivation in HIV-1 latently infected monocytic cells (TH89GFP, U1) and microglial cells (HC69). LSM also inhibited HIV infection in human induced pluripotent stem cell (iPSC) derived microglia (iMG), primary human resident liver macrophages (Kupffer cells) as well as human monocyte-derived macrophages (MDMs). Furthermore, we demonstrated that overexpression of a predicted drug target of LSM, the conserved serine/threonine kinase RIOK1 (RIO kinase 1), overcomes LSMs anti-HIV effect. Overall, our studies concluded that LSM is a promising LPA to inhibit HIV-1 infection in myeloid cells in the RIOK1-dependent manner.

microbiology↗

bioRxiv2026

Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV2 positive B-cell lymphomas

Summary/AbstractHistone methylation is a dynamic and reversible epigenetic modification that critically controls the progression of human diseases, including infections and cancers. Here we reported that histone lysine demethylases (KDMs) in the KDM5 family KDM5A/B play profound roles in suppressing lytic reactivation of oncogenic human herpesvirus 8 (HHV-8), i.e., Kaposis sarcoma-associated herpesvirus (KSHV), as well as antiviral/antitumor innate immune responses in KSHV-infected B-cell lymphomas. We showed that KSHV lytic replication decreases KDM5A/B protein stability by enhancing their K-48 linked polyubiquitination while KDM5A/B depletion facilitates KSHV lytic reactivation. Mechanistic studies illustrated that KDM5A/B associate with KSHV LANA protein and dampen its chromatin association at both KSHV viral lytic promoter and promoters of antitumor immune-responsive genes (IRGs). In comparisons to normal B cells, KDM5A/B expression significantly increased in B-cell lymphoma cells, including KSHV-positive primary effusion lymphoma (PEL). We demonstrated that KDM5A/B inhibition remarkably induces both KSHV lytic reactivation and innate immune responses in PEL cells, resulting in a strong viral oncolytic effect, both in vitro in cell cultures and in vivo using a PEL xenograft mouse model. Overall, our studies identified the novel functions of KDM5A/B to silence KSHV lytic replication and antiviral/antitumor innate immune responses, which can be blocked to benefit the treatment of KSHV-associated B-cell lymphomas that are usually aggressive and difficult to treat.

microbiology↗

bioRxiv2025

NAT10 Suppresses RNA Sensing Induced IFN-β Transactivation to Promote Viral Infection via Interfering with IRF3 Activities

Cells can sense invading viruses and trigger type I interferons (IFN-/{beta}) to evoke antiviral innate immune response. Induction of IFNs needs to be fine-tuned to achieve the antiviral consequence while avoiding severe disruption of host cell homeostasis. Here, we reported that NAT10, the acetyltransferase of histone and N4-acetylcytidine (ac4C) RNA modification, promotes infection of RNA viruses via regulation of type I IFN signaling. Depletion of NAT10 increased the expression of IFN-{beta} and interferon-stimulated genes (ISGs) upon stimulation of type I IFN antiviral signaling, while it impaired viral replication. NAT10 dynamically associated with the IFN-{beta} promotor and negatively regulated IRF3 through modulation of long non-coding RNAs (lncRNAs) that inhibit IRFs. Consistently, the small molecule inhibitor of NAT10, Remodelin, increased IFN-{beta} expression while inhibiting viral infections. Overall, our findings indicated that NAT10 is a negative regulator of type I IFN signaling, suggesting its potential as a target of antiviral treatment.

microbiology↗