The landscape of lncRNAs in gastric cancer: from molecular mechanisms to potential clinical applications.

Gastric cancer (GC) is a highly prevalent and deadly malignant neoplasm worldwide. Currently, long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators implicated in GC development and progression. Dysregulated expression of lncRNAs is commonly associated with enhanced tumor migration, invasiveness, and therapy resistance, highlighting their potential as promising targets for clinical applications. This review offers a comprehensive historical overview of lncRNAs in GC, describes the molecular mechanisms, and discusses the prospects and challenges of establishing lncRNAs as precision biomarkers.

Revealing metastatic castration-resistant prostate cancer master regulator through lncRNAs-centered regulatory network.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive form of cancer unresponsive to androgen deprivation therapy (ADT) that spreads quickly to other organs. Despite reduced androgen levels after ADT, mCRPC development and lethality continues to be conducted by the androgen receptor (AR) axis. The maintenance of AR signaling in mCRPC is a result of AR alterations, androgen intratumoral production, and the action of regulatory elements, such as noncoding RNAs (ncRNAs). ncRNAs are key elements in cancer signaling, acting in tumor growth, metabolic reprogramming, and tumor progression. In prostate cancer (PCa), the ncRNAs have been reported to be associated with AR expression, PCa proliferation, and castration resistance. In this study, we aimed to reconstruct the lncRNA-centered regulatory network of mCRPC and identify the lncRNAs which act as master regulators (MRs). METHODS: We used publicly available RNA-sequencing to infer the regulatory network of lncRNAs in mCRPC. Five gene signatures were employed to conduct the master regulator analysis. Inferred MRs were then subjected to functional enrichment and symbolic regression modeling. The latter approach was applied to identify the lncRNAs with greater predictive capacity and potential as a biomarker in mCRPC. RESULTS: We identified 31 lncRNAs involved in cellular proliferation, tumor metabolism, and invasion-metastasis cascade. SNHG18 and HELLPAR were the highlights of our results. SNHG18 was downregulated in mCRPC and enriched to metastasis signatures. It accurately distinguished both mCRPC and primary CRPC from normal tissue and was associated with epithelial-mesenchymal transition (EMT) and cell-matrix adhesion pathways. HELLPAR consistently distinguished mCRPC from primary CRPC and normal tissue using only its expression. CONCLUSION: Our results contribute to understanding the regulatory behavior of lncRNAs in mCRPC and indicate SNHG18 and HELLPAR as master regulators and potential new diagnostic targets in this tumor.

Morphological tongue and palate characterizations in Trachemys adiutrix (Vanzolini, 1995) turtles.

Morphological studies on the oropharyngeal cavity of turtles are an interesting tool in understanding evolutionary processes associated with feeding habits. There is paucity of morphological information on the oropharyngeal cavity of the Trachemys adiutrix turtle. Thus, the aim of this study was to describe the tongue and palate morphology of T. adiutrix to establish a standard model for the species, providing information that may improve knowledge on the species feeding habits. Gross dissection, light microscopy and scanning electron microscopy assessments of 11 specimens were carried out. The tongue of T. adiutrix is triangular with a slightly rounded apex and broad base and lingual papillae widely distributed throughout the entire dorsal surface. The palate is composed of bony structures, displaying a triangular apex with one pair of choanae and palatine raphe that begin in the middle region, dividing the two openings. The body was elongated and smooth. The root was wrinkled and opened into the oesophagus. The tongue was lined by non-keratinized stratified squamous epithelium, rich in mucous cells and a large number of different-shaped papillae and taste buds. The palate was mainly lined by a pseudostratified cylindrical ciliated epithelium rich in mucous cells. In conclusion, the tongue and palate characteristics of T. adiutrix include evidence that these animals are semiaquatic, displaying morphological characteristics associated with aquatic and terrestrial trophic ecology, similar to that observed in other semiaquatic and terrestrial chelonian species.

Global miRNA expression reveals novel nuclear and mitochondrial interactions in Type 1 diabetes mellitus.

Background: Considering the potential role of miRNAs as biomarkers and their interaction with both nuclear and mitochondrial genes, we investigated the miRNA expression profile in type 1 diabetes (T1DM) patients, including the pathways in which they are involved considering both nuclear and mitochondrial functions. Methods: We analyzed samples of T1DM patients and control individuals (normal glucose tolerance) by high throughput miRNA sequencing (miRNome). Next, five miRNAs - hsa-miR-26b-5p, hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p and hsa-miR-100-5p - were validated by RT-qPCR. The identification of target genes was extracted from miRTarBase and mitoXplorer database. We also performed receiver operating characteristic (ROC) curves and miRNAs that had an AUC > 0.85 were considered potential biomarkers. Results: Overall, 41 miRNAs were differentially expressed in T1DM patients compared to control. Hsa-miR-21-5p had the highest number of predicted target genes and was associated with several pathways, including insulin signaling and apoptosis. 34.1% (14/41) of the differentially expressed miRNAs also targeted mitochondrial genes, and 80.5% (33/41) of them targeted nuclear genes involved in the mitochondrial metabolism. All five validated miRNAs were upregulated in T1DM. Among them, hsa-miR-26b-5p showed AUC>0.85, being suggested as potential biomarker to T1DM. Conclusion: Our results demonstrated 41 DE miRNAs that had a great accuracy in discriminating T1DM and control group. Furthermore, we demonstrate the influence of these miRNAs on numerous metabolic pathways, including mitochondrial metabolism. Hsa-miR-26b-5p and hsa-miR-21-5p were highlighted in our results, possibly acting on nuclear and mitochondrial dysfunction and, subsequently, T1DM dysregulation.

Comprehensive analysis of germline mutations in northern Brazil: a panel of 16 genes for hereditary cancer-predisposing syndrome investigation.

BACKGROUND: Next generation sequencing (NGS) has been a handy tool in clinical practice, mainly due to its efficiency and cost-effectiveness. It has been widely used in genetic diagnosis of several inherited diseases, and, in clinical oncology, it may enhance the discovery of new susceptibility genes and enable individualized care of cancer patients. In this context, we explored a pan-cancer panel in the investigation of germline variants in Brazilian patients presenting clinical criteria for hereditary cancer syndromes or familial history. METHODS: Seventy-one individuals diagnosed or with familial history of hereditary cancer syndromes were submitted to custom pan-cancer panel including 16 high and moderate penetrance genes previously associated with hereditary cancer syndromes (APC, BRCA1, BRCA2, CDH1, CDKN2A, CHEK2, MSH2, MSH6, MUTYH, PTEN, RB1, RET, TP53, VHL, XPA and XPC). All pathogenic variants were validated by Sanger sequencing. RESULTS: We identified a total of eight pathogenic variants among 12 of 71 individuals (16.9%). Among the mutation-positive subjects, 50% were diagnosed with breast cancer and had mutations in BRCA1, CDH1 and MUTYH. Notably, 33.3% were individuals diagnosed with polyposis or who had family cases and harbored pathogenic mutations in APC and MUTYH. The remaining individuals (16.7%) were gastric cancer patients with pathogenic variants in CDH1 and MSH2. Overall, 54 (76.05%) individuals presented at least one variant uncertain significance (VUS), totalizing 81 VUS. Of these, seven were predicted to have disease-causing potential. CONCLUSION: Overall, analysis of all these genes in NGS-panel allowed the identification not only of pathogenic variants related to hereditary cancer syndromes but also of some VUS that need further clinical and molecular investigations. The results obtained in this study had a significant impact on patients and their relatives since it allowed genetic counselling and personalized management decisions.