ROBO3 (Roundabout Guidance Receptor 3)

Combination treatment with XCT790 and endocrine therapies, including the ERα antagonist Tamoxifen or degrader Fulvestrant, produced synergistic antitumor effects. In addition, XCT790 treatment augmented the therapeutic efficacy of chemotherapeutic agents such as Doxorubicin in suppressing ERα-positive breast cancer cell growth both in vitro and in vivo. In summary, our findings reveal that ESRRA is a pivotal regulator of ERSEs and estrogen/ERα-target gene activation, as well as the type I IFN signaling pathway, highlighting its potential as a promising therapeutic target in ERα-positive breast cancer in the clinic.

Furthermore, we discovered that ROBO3 enhances the secretion of chemokines CCL2 and CCL5 in ESCs, which subsequently promote macrophage polarization toward the M2 phenotype, as indicated through elevated expression of interleukin-10 and Arg-1. Collectively, our findings elucidate a dual mechanism whereby ROBO3 drives endometriosis progression through both intrinsic activation of Wnt/β-catenin signaling and extrinsic modulation of tumor-associated macrophages, underscoring ROBO3 as a promising therapeutic target for endometriosis.

Our study presents a methodology to identify novel candidate immunotherapy targets. We also use known genomic data to identify subtype-specific targets that could be used either as complementary or alternative targets to existing treatments. We show that immunotherapy targets can have heterogenous expression within a patient, which can affect treatment efficacy. Taken together, our study establishes a robust methodology to identify novel therapeutic targets in MM, revealing critical insights that will inform the development of current and next-generation immunotherapies.

Finally, a multi-step analysis was conducted to identify two pivotal hub genes, PKM and ITGA3, in the high-scoring group of BMRGs, which exhibited significant associations with an unfavorable prognosis in HCC. Our study suggests that the BMRGs score can serve as a robust biomarker for predicting clinical outcomes and evaluating the tumor microenvironment in patients with HCC, thereby facilitating more effective clinical implementation of immunotherapy.

The findings of this study provide insights into transcriptome expression and regulation which may better explain complex thermal resilience mechanism of Tharparkar cattle in heat stress under natural conditions. The online version contains supplementary material available at 10.1007/s13205-024-04018-2.

In this first GWAS exploring propofol requirements, we discovered novel genetic associations suggesting new biologically relevant pathways for propofol and general anesthesia. The roles of the gene products of ROBO3/FEZ1, NALCN and KCNJ2 in propofol anesthesia warrant further studies.

The analysis of duplications and deletions in the DCC should be included in the routine genetic diagnostic evaluation of patients with suspected HGPPS2. This report expands the knowledge of phenotypic and genotypic spectrum of pathogenic variants causing HGPPS2.

Moreover, RT-qPCR, Western blotting, and immunocytochemistry confirmed the relatively minor adaptations to the hugely different dsRNA levels. As a consequence, these transformed cell lines are potentially less tolerant to interventions that increase the formation of endogenous dsRNA.

Our results provide novel data highlighting the unique aspects of the RVC-associated host cellular signalling and suggest that increased upregulation of the key antiviral factors maybe one of the mechanisms responsible for RVC age-specific characteristics and its inability to replicate in most cell cultures.

Our studies demonstrated the existence of novel increased expression of genes encoding surface proteins in NDMM patient samples that maintained their expression levels or increased when being exposed to existing standard of care in MM. In some instances, these genes associate with existing cytogenetic subgroups and may serve as novel proteins that can be further targeted by immune-related therapies.

In addition, full-length DCC in collaboration with ROBO3 can antagonize ROBO1 repulsion in vivo. We propose that commissural axons integrate and balance the opposing DCC and Roundabout (ROBO) signaling to ensure proper guidance decisions during midline entry and exit.