Commentary – CRISPR-based techniques: Cas9, Cas13 and their applications in the era of COVID-19

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/ Cas9 (CRISPR-associated protein 9) system enables scientists to edit diverse genome types with relative ease, with the aim – in the near future – to prevent future human beings from developing genetic diseases. The new opportunities arising from the system are broad-ranging and revolutionary, but such prospects have also been the cause for alarm throughout the international scientific community. The authors have laid out a review of the trials carried out so far in terms of genome editing, for the ultimate purpose of weighing implications and criticisms. We feel that possible valuable alternatives, such as induced pluripotent stem cells should not be overlooked

Incidence of temporomandibular joint clicking in adolescents with and without unilateral posterior cross-bite: a 10-year follow-up study

Among different malocclusions, posterior cross-bite is thought to have a strong impact on the correct functioning of the masticatory system. The association between unilateral posterior cross-bite (UPCB) and temporomandibular joint (TMJ) clicking, however, remains still controversial. The aim of this study was to investigate whether the presence of UCPB during early adolescence increases the risk of reporting TMJ clicking after a long-term follow-up. A longitudinal survey design was carried out in a group of 12-year-old young adolescents, who were examined at baseline for TMJ clicking sounds and unilateral posterior cross-bite. After 10 years, 519 subjects could be reached by a telephone survey. Standardised questions were used to collect self-reported TMJ sounds and to determine whether participants had received an orthodontic treatment. Logistic regression analysis revealed a significant association between unilateral posterior cross-bite and subjectively reported TMJ clicking (odds ratio = 6·0; 95% confidence limits = 3·4-10·8; P < 0·0001). The incidence of TMJ clicking was 12%. At a ten-year follow-up, self-reports of TMJ clicking were significantly associated with the presence of UPCB at baseline, but not with the report of having received an orthodontic treatment. Within the limitation of this study, the presence of unilateral posterior cross-bite in young adolescents may increase the risk of reporting TMJ sounds at a 10-year follow-up. The provision of an orthodontic treatment, however, does not appear to reduce the risk of reporting TMJ sounds

Contextualizing the Genes Altered in Bladder Neoplasms in Pediatric and Teen Patients Allows Identifying Two Main Classes of Biological Processes Involved and New Potential Therapeutic Targets

Research on bladder neoplasms in pediatric and teen patients (BNPTP) has described 21 genes, which are variously involved in this disease and are mostly responsible for deregulated cell proliferation. However, due to the limited number of publications on this subject, it is still unclear what type of relationships there are among these genes and which are the chances that, while having different molecular functions, they i) act as downstream effector genes of well-known pro- or anti- proliferative stimuli and/or interplay with biochemical pathways having oncological relevance or ii) are specific and, possibly, early biomarkers of these pathologies. A Gene Ontology (GO)-based analysis showed that these 21 genes are involved in biological processes, which can be split into two main classes: cell regulation-based and differentiation/development-based. In order to understand the involvement/overlapping with main cancer-related pathways, we performed a meta-analysis dependent on the 189 oncogenic signatures of the Molecular Signatures Database (OSMSD) curated by the Broad Institute. We generated a binary matrix with 53 gene signatures having at least one hit; this analysis i) suggests that some genes of the original list show inconsistencies and might need to be experimentally re- assessed or evaluated as biomarkers (in particular, ACTA2) and ii) allows hypothesizing that important (proto)oncogenes (E2F3, ERBB2/HER2, CCND1, WNT1, and YAP1) and (putative) tumor suppressors (BRCA1, RBBP8/CTIP, and RB1-RBL2/p130) may participate in the onset of this disease or worsen the observed phenotype, thus expanding the list of possible molecular targets for the treatment of BNPTP

Oncogenic roles of GOLPH3 in the physiopathology of cancer

Golgi phosphoprotein 3 (GOLPH3), un effettore del fosfatidilinositolo 4-fosfato [PI (4) P] al Golgi, è necessaria per il mantenimento della struttura del nastro del Golgi, il traffico di vescicole e la glicosilazione del Golgi. GOLPH3 è stato convalidato come oncoproteina combinando la genomica integrativa con l'analisi clinopatologiche e funzionali. È spesso amplificato in diversi tipi di tumori solidi tra cui melanoma, cancro ai polmoni, cancro al seno, glioma e cancro del colon-retto. La sovraespressione di GOLPH3 è correlata a una prognosi infausta in più tipi di tumore, compreso il 52% dei tumori al seno e dal 41% al 53% del glioblastoma. I ruoli di GOLPH3 nella tumorigenesi possono essere correlati a diverse attività cellulari, tra cui: (i) regolazione del traffico dal Golgi alla membrana plasmatica e contributo a fenotipi secretori maligni; (ii) controllare l'internalizzazione e il riciclaggio di molecole di segnalazione chiave o aumentare la glicosilazione delle glicoproteine ​​rilevanti per il cancro; e (iii) influenzare la risposta al danno al DNA e il mantenimento della stabilità genomica. Qui riassumiamo le attuali conoscenze sui percorsi oncogeni che coinvolgono GOLPH3 nel cancro umano, l'influenza di GOLPH3 sul metabolismo del tumore e sullo stroma circostante e il suo possibile ruolo nella formazione di metastasi tumorali.Golgi phosphoprotein 3 (GOLPH3), a Phosphatidylinositol 4-Phosphate [PI(4)P] effector at the Golgi, is required for Golgi ribbon structure maintenance, vesicle trafficking and Golgi glycosylation. GOLPH3 has been validated as an oncoprotein through combining integrative genomics with clinopathological and functional analyses. It is frequently amplified in several solid tumor types including melanoma, lung cancer, breast cancer, glioma, and colorectal cancer. Overexpression of GOLPH3 correlates with poor prognosis in multiple tumor types including 52% of breast cancers and 41% to 53% of glioblastoma. Roles of GOLPH3 in tumorigenesis may correlate with several cellular activities including: (i) regulating Golgi-to-plasma membrane trafficking and contributing to malignant secretory phenotypes; (ii) controlling the internalization and recycling of key signaling molecules or increasing the glycosylation of cancer relevant glycoproteins; and (iii) influencing the DNA damage response and maintenance of genomic stability. Here we summarize current knowledge on the oncogenic pathways involving GOLPH3 in human cancer, GOLPH3 influence on tumor metabolism and surrounding stroma, and its possible role in tumor metastasis formation

Y RNA: an overview of their role as potential biomarkers and molecular targets in human cancers

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients

Non-coding RNAs as prognostic markers for endometrial cancer

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs

COG7 deficiency in Drosophila generates multifaceted developmental, behavioral and protein glycosylation phenotypes

Congenital disorders of glycosylation (CDG) comprise a family of human multisystemic diseases caused by recessive mutations in genes required for protein N-glycosylation. More than 100 distinct forms of CDGs have been identified and most of them cause severe neurological impairment. The Conserved Oligomeric Golgi (COG) complexmediates tethering of vesicles carrying glycosylation enzymes across the Golgi cisternae. Mutations affecting human COG1, COG2 and COG4-COG8 cause monogenic forms of inherited, autosomal recessive CDGs.We have generated a Drosophila COG7-CDG model that closely parallels the pathological characteristics of COG7-CDG patients, including pronounced neuromotor defects associated with altered N-glycome profiles. Consistent with these alterations, larval neuromuscular junctions of Cog7 mutants exhibit a significant reduction in bouton numbers. We demonstrate that the COG complex cooperates with Rab1 and Golgi phosphoprotein 3 to regulate Golgi trafficking and that overexpression of Rab1 can rescue the cytokinesis and locomotor defects associated with loss of Cog7. Our results suggest that the Drosophila COG7-CDG model can be used to test novel potential therapeutic strategies by modulating trafficking pathways

Towards personalized medicine: Non-coding rnas and endometrial cancer

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse

Non-coding RNAs and endometrial cancer

Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular