The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5′-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5′-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.

Introduction: Breast cancer represents a heterogeneous group of tumors characterized by diverse molecular and clinical features, driven by both genetic alterations and epigenetic regulation. Among these mechanisms, the Hedgehog (Hh) developmental pathway, particularly elevated levels of its ligand Sonic Hedgehog (SHH), has been implicated in breast cancer progression. Methyltransferase-like 3 (METTL3), the core catalytic component of the m6A methyltransferase complex, responsible for N6-methyladenosine (m6A) modification of mRNA, has shown a stronger prognostic relevance in regulating mRNA stability and cancer development than other m6A writers, erasers, or readers. Despite evidence suggesting that both SHH and METTL3 contribute to tumor growth in breast tissue, the functional relationship between these factors remains unclear. In this study, we investigated the potential of the METTL3-SHH axis in breast cancer progression to address this gap.Methods: We have performed bioinformatic analyses by utilizing data from UALCAN, cBioPortal, and GEPIA platforms to comprehensively investigate the methylation patterns, gene expression levels, and mutation profiles of specific genes of interest. Expressions of METTL3 and components of the SHH signaling pathway were analyzed by qRT-PCR. Statistical analyses were performed by using Student’s t-test, Spearman and Pearson coefficient (r) test, ANOVA test, and log–rank test.Results: Analysis of 35 breast cancer patients of Bangladesh and gene expression data from The Cancer Genome Atlas (n = 1,021) database revealed METTL3 is overexpressed in breast cancer, and upregulation of METTL3 and downstream key components of the SHH signaling pathway (p < 0.05 vs. control) correlates significantly with worse patient outcomes (HR = 1.3). These findings suggest a possible regulatory mechanism linking METTL3-mediated m6A modification to SHH signaling in breast cancer progression. Elucidating this axis could provide novel insights into tumor biology and identify promising targets for epigenetic therapies.

Mitochondrial succinate dehydrogenase subunits are differentially expressed in multiple tumor types, suggesting their role as a cancer type-dependent metabolic target. However, information on the expression of SDH subunits in breast cancer (BC), particularly in South Asian populations, remains scarce. So, we analyze the expression profile of all four SDH subunits in breast cancer patients from Bangladesh. qRT-PCR was carried out to analyze the mRNA expression of four SDH subunits in Luminal A, Luminal B, Her2+, and triple-negative breast cancer subtypes and the results were compared with The Cancer Genome Atlas (TCGA) database. All four succinate dehydrogenase subunits were significantly upregulated in tumor tissues when compared to controls and showed an alignment with the TCGA except SDHD, which was significantly downregulated in TCGA. Subtype-specific analysis demonstrated differential expression patterns. SDHD upregulation has also been connected to worse outcomes for patients which indicates its role in cancer progression. Furthermore, we found a significant upregulation of METTL3 in our patient cohort. Taken together, the elevated SDHD and METTL3 expression suggests a potential epigenetic mechanism-driven SDHD activation, highlighting its previously unreported role in breast cancer biology and revealing a distinct pattern of SDH dysregulation in the Bangladeshi breast cancer population.