CRNDE is considered an oncogene expressed as long non-coding RNA. Our previous paper is the only one reporting CRNDE as a micropeptide-coding gene. The amino acid sequence of this micropeptide (CRNDEP) has recently been confirmed by other researchers. This study aimed at providing a mass spectrometry (MS)-based validation of the CRNDEP sequence and an investigation of how the differential expression of CRNDE(P) influences the metabolism and chemoresistance of ovarian cancer (OvCa) cells. We also assessed cellular localization changes of CRNDEP, looked for its protein partners, and bioinformatically evaluated its RNA-binding capacities. Herein, we detected most of the CRNDEP sequence by MS. Moreover, our results corroborated the oncogenic role of CRNDE, portraying it as the gene impacting carcinogenesis at the stages of DNA transcription and replication, affecting the RNA metabolism, and stimulating the cell cycle progression and proliferation, with CRNDEP being detected in the centrosomes of dividing cells. We also showed that CRNDEP is located in nucleoli and revealed interactions of this micropeptide with p54, an RNA helicase. Additionally, we proved that high CRNDE(P) expression increases the resistance of OvCa cells to treatment with microtubule-targeted cytostatics. Furthermore, altered CRNDE(P) expression affected the activity of the microtubular cytoskeleton and the formation of focal adhesion plaques. Finally, according to our in silico analyses, CRNDEP is likely capable of RNA binding. All these results contribute to a better understanding of the CRNDE(P) role in OvCa biology, which may potentially improve the screening, diagnosis, and treatment of this disease.

CRNDE is an oncogene expressed as a long non-coding RNA. However, our team previously reported that the CRNDE gene also encodes a micropeptide, CRNDEP. The amino acid sequence of CRNDEP has recently been revealed by other researchers, too. This study aimed to investigate genetic alterations within the CRNDEP-coding region of the CRNDE gene, methylation profiling of this gene, and CRNDEP expression analysis. All investigations were performed on clinical material from patients with ovarian tumors of diverse aggressiveness. We found that CRNDEP levels were significantly elevated in highly aggressive tumors compared to benign neoplasms. Consistently, a high level of this micropeptide was a negative, independent, prognostic, and predictive factor in high-grade ovarian cancer (hgOvCa) patients. The cancer-promoting role of CRNDE(P), shown in our recent study, was also supported by genetic and epigenetic results obtained herein, revealing no CRNDEP-disrupting mutations in any clinical sample. Moreover, in borderline ovarian tumors (BOTS), but not in ovarian cancers, the presence of a single nucleotide polymorphism in CRNDE, rs115515594, significantly increased the risk of recurrence. Consistently, in BOTS only, the same genetic variant was highly overrepresented compared to healthy individuals. We also discovered that hypomethylation of CRNDE is associated with increased aggressiveness of ovarian tumors. Accordingly, hypomethylation of this gene’s promoter/first exon correlated with hgOvCa resistance to chemotherapy, but only in specimens with accumulation of the TP53 tumor suppressor protein. Taken together, these results contribute to a better understanding of the role of CRNDE(P) in tumorigenesis and potentially may lead to improvements in screening, diagnosis, and treatment of ovarian neoplasms.

Borderline ovarian tumors (BOTS) are rare neoplasms of intermediate aggressiveness between cystadenomas and low-grade ovarian cancers (lgOvCa), which they share some molecular resemblances with. In contrast to the most frequent and well-described high-grade ovarian carcinomas (hgOvCa), the molecular background of BOTS and lgOvCa is less thoroughly characterized. Here, we aimed to analyze genetic variants in crucial tumor suppressors and oncogenes in BOTS (with or without the BRAF V600E mutation), lgOvCa, and hgOvCa in two gene panels using next-generation sequencing. Then, we verified the existence of selected polymorphisms by Sanger sequencing. Finally, Western blot analyses were carried out to check the impact of the selected polymorphisms on the expression of the corresponding proteins. Our study contributes to the molecular characterization of ovarian neoplasms, demonstrating divergent polymorphic patterns pointing to distinct signaling pathways engaged in their development. Certain mutations seem to play an important role in BOTS without the BRAF V600E variant (KRAS) and in lgOvCa (KRAS and NRAS), but not in hgOvCa. Additionally, based on multivariable regression analyses, potential biomarkers in BOTS (PARP1) and hgOvCa (FANCI, BRCA2, TSC2, FANCF) were identified. Noteworthy, for some of the analyzed genes, such as FANCI, FANCD2, and FANCI, FANCF, TSC2, the status of BRCA1/2 and TP53, respectively, turned out to be crucial. Our results shed new light on the similarities and differences in the polymorphic patterns between ovarian tumors of diverse aggressiveness. Furthermore, the biomarkers identified herein are of potential use as predictors of the prognosis and/or response to therapy.

Background: Changes in DNA methylation patterns are a pivotal mechanism of carcinogenesis. In some tumors, aberrant methylation precedes genetic changes, while gene expression may be more frequently modified due to methylation alterations than by mutations. Methods: Herein, 128 serous ovarian tumors were analyzed, including borderline ovarian tumors (BOTS) with (BOT.V600E) and without (BOT) the BRAF V600E mutation, low-grade (lg), and high-grade (hg) ovarian cancers (OvCa). The methylome of the samples was profiled with Infinium MethylationEPIC microarrays. Results: The biggest number of differentially methylated (DM) CpGs and regions (DMRs) was found between lgOvCa and hgOvCa. By contrast, the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups and, in relation to BOT, their genome was strongly downmethylated. Remarkably, the ten most significant DMRs, discriminating BOT from lgOvCa, encompassed the MHC region on chromosome 6. We also identified hundreds of DMRs, being of potential use as predictive biomarkers in BOTS and hgOvCa. DMRs with the best discriminative capabilities overlapped the following genes: BAIAP3, IL34, WNT10A, NEU1, SLC44A4, and HMOX1, TCN2, PES1, RP1-56J10.8, ABR, NCAM1, RP11-629G13.1, AC006372.4, NPTXR in BOTS and hgOvCa, respectively. Conclusions: The global genome-wide hypomethylation positively correlates with the increasing aggressiveness of ovarian tumors. We also assume that the immune system may play a pivotal role in the transition from BOTS to lgOvCa. Given that the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups, when methylome is considered, such tumors might be placed in-between BOT and OvCa.

Domestic cats are among the most popular companion animals worldwide, with steadily increasing ownership and life expectancy. Paradoxically, despite their high prevalence and shared environmental exposures with humans, cats remain markedly underrepresented in molecular oncology research. Cancer is a leading cause of feline mortality, and alimentary lymphoma (AL) has emerged as one of the most common feline malignancies, yet its molecular landscape remains poorly characterized. This review summarizes current knowledge on feline AL, including epidemiology, risk factors, classification schemes, diagnostic challenges, treatment outcomes, and survival, with particular emphasis on low-grade alimentary lymphoma (LGAL), the most prevalent subtype. We discuss the complex relationship between chronic inflammatory enteropathies and lymphoma, highlighting diagnostic ambiguities and the inflammatory–neoplastic continuum. Importantly, we provide a critical overview of existing genomic, transcriptomic, epigenomic, proteomic, and metabolomic studies in feline AL, revealing a striking paucity of high-throughput, multi-omics analyses based on clinical material. Recent advances in feline genome assembly and annotation offer new opportunities to address these gaps. Furthermore, we compare feline AL with its human gastrointestinal T-cell lymphoma counterparts, demonstrating substantial molecular homology across key oncogenic pathways, including JAK/STAT signaling. This comparative perspective underscores the potential of feline AL as a naturally occurring model for the human disease. We conclude that comprehensive molecular characterization of feline AL is urgently needed to improve diagnostics, prognostication, and targeted therapies, with likely translational benefits for both veterinary and human oncology. Aim: The goal of this review is to summarize the current knowledge on feline alimentary lymphoma, including its origin, risk, classification, treatment approaches, and especially molecular landscape, which still remains poorly investigated with modern high-throughput techniques.

Although progress has been made in developing new therapies and deepening the biological understanding of ovarian carcinoma (OvCa), it continues to be the most lethal gynecologic cancer in women