Showing papers by "Carlo M. Croce published in 2022"
TL;DR: The findings strongly suggest that small non-coding RNAs could function as biomarkers and possible targets for therapy and assess their potential clinical implications.
Abstract: Simple Summary Leukemia is a group of blood cancers that arise when abnormal or underdeveloped blood cells accumulate in the bloodstream, bone marrow and lymphatic system. A driver event in the development of Chronic Lymphocytic Leukemia (CLL) is the deletion of the genomic region encoding for miR-15a/16-1. MicroRNAs are small non-coding RNAs involved in the regulation of gene expression, and loss of miR-15a/16-1 in CLL results in the accumulation of the antiapoptotic gene BCL2 and inhibition of the apoptotic process. This discovery was the first evidence that microRNAs have a role in the onset of cancer. Following this finding, several studies investigated the role of microRNAs and other small non-coding RNAs in different types of leukemia and cancers in general. This review summarizes the role of small non-coding RNAs in leukemia and describes their possible application in clinical settings as biomarkers and/or targets for therapy. Abstract In 2020, more than 60,500 people were diagnosed with leukemia in the USA, and more than 23,000 died. The incidence of leukemia is still rising, and drug resistance development is a serious concern for patients’ wellbeing and survival. In the past two decades, small non-coding RNAs have been studied to evaluate their functions and possible role in cancer pathogenesis. Small non-coding RNAs are short RNA molecules involved in several cellular processes by regulating the expression of genes. An increasing body of evidence collected by many independent studies shows that the expression of these molecules is tissue specific, and that their dysregulation alters the expression of genes involved in tumor development, progression and drug response. Indeed, small non-coding RNAs play a pivotal role in the onset, staging, relapse and drug response of hematological malignancies and cancers in general. These findings strongly suggest that small non-coding RNAs could function as biomarkers and possible targets for therapy. Thus, in this review, we summarize the regulatory mechanisms of small non-coding RNA expression in different types of leukemia and assess their potential clinical implications.
4 citations
TL;DR: The possibility of examining embedded EVs as substrates to be used for detecting DNA amplification through ultrasensitive in situ hybridization (ISH) is shown, which allows the visualization of DNA targets in a more direct manner, without time consuming optimization steps or particular expertise.
Abstract: Abstract EVs have emerged as an important component in tumour initiation, progression and metastasis. Although notable progresses have been made, the detection of EV cargoes remain significantly challenging for researchers to practically use; faster and more convenient methods are required to validate the EV cargoes, especially as biomarkers. Here we show, the possibility of examining embedded EVs as substrates to be used for detecting DNA amplification through ultrasensitive in situ hybridization (ISH). This methodology allows the visualization of DNA targets in a more direct manner, without time consuming optimization steps or particular expertise. Additionally, formalin‐fixed paraffin‐embedded (FFPE) blocks of EVs allows long‐term preservation of samples, permitting future studies. We report here: (i) the successful isolation of EVs from liposarcoma tissues; (ii) the EV embedding in FFPE blocks (iii) the successful selective, specific ultrasensitive ISH examination of EVs derived from tissues, cell line, and sera; (iv) and the detection of MDM2 DNA amplification in EVs from liposarcoma tissues, cell lines and sera. Ultrasensitive ISH on EVs would enable cargo study while the application of ISH to serum EVs, could represent a possible novel methodology for diagnostic confirmation. Modification of probes may enable researchers to detect targets and specific DNA alterations directly in tumour EVs, thereby facilitating detection, diagnosis, and improved understanding of tumour biology relevant to many cancer types.
3 citations
TL;DR: The importance of going beyond the well-established paradigm of one mature miRNA per miRNA arm to elucidate novel mechanisms related to cancer progression is outlined, and a shifted and edited miRNA isoform was experimentally validated to directly bind and suppress a unique target.
Abstract: Modified miRNAs may act as cancer biomarkers and function as allies or antagonists of their canonical counterparts in gene regulation, suggesting the concurrent consideration of canonical and modified miRNAs can boost patient stratification.
2 citations
TL;DR: MiR-15/16 is a key tumor suppressor microRNA cluster first identified as a target of 13q deletions in CLL and a recent report demonstrated that miR-16 regulates PD-L1 expression in prostate and other cancers, which provided the first evidence of the involvement of noncoding RNAs in cancer pathogenesis.
2 citations
TL;DR: TRNA fragments (tRNA derived fragments or tRFs) are small single stranded RNA molecules derived from pre-tRNAs and mature tRNAs as mentioned in this paper and have been known for a number of years, but previously they were believed to be not important products of tRNA degradation.
Abstract: tRNA fragments (tRNA derived fragments or tRFs) are small single stranded RNA molecules derived from pre-tRNAs and mature tRNAs. tRFs have been known for a number of years, but previously they were believed to be not important products of tRNA degradation. tRFs can be unique, like tRF-1 s, or redundant, like tRF-3 s and tRF-5 s. Scientific interest in tRFs has drastically increased in the last 5 years. Many studies have found that tRFs are differentially expressed in many normal cellular processes as well as in transformed cancer cells. Dysregulation of tRFs expression have been reported in multiple major types of cancer including solid cancers and lymphoid malignancies. However the exact molecular role of these molecules is not entirely clear. A number of studies proposed that tRFs can work as microRNAs by targeting gene expression. Here we discuss recent studies showing differential expression of tRFs in many cancers as well as what is currently known about tRFs biological functions in cancer cells.
2 citations
TL;DR: It is shown that microdeletions affecting the miR-15a/16-1 cluster are more frequent than expected in all CLL cohorts and are prevalent in patients carrying a trisomy 12, and copy-number variation analysis and an experimental FISH analysis revealed that ∼34% of samples carry previously unidentified micro deletions ofMiR- 15a/ 16-1, which may have clinical relevance for the successful stratification of patients for treatment.
Abstract: Significance 13q14.3 deletion is the most common genetic lesion identified in CLLs. This study shows that microdeletions affecting the miR-15a/16-1 cluster are more frequent than expected in all CLL cohorts and are prevalent in patients carrying a trisomy 12. Copy-number variation analysis and an experimental FISH analysis revealed that ∼34% of samples carry previously unidentified microdeletions of miR-15a/16-1. These data may have clinical relevance for the successful stratification of patients for treatment. Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is characterized by chromosomal aberrations including 13q, 11q, and 17p deletions and a trisomy of chromosome 12 (T12). 13q deletions are often associated with 11q and 17p deletions in aggressive cases. Conversely, T12 CLLs show a variable prognosis, and association with 13q deletions is uncommon. The miR-15a/16-1 cluster is the functional target of 13q deletions, leading to BCL2 overexpression. Chromosomal aberrations in CLL are associated with prognosis, and their identification is carried out by fluorescence in situ hybridization (FISH). Since standard FISH only detects large deletions, we investigated the presence of undetected microdeletions targeting miR-15a/16-1 in CLL cases. We found that ∼34% of CLL samples show an unreported loss of the miR-15a/16-1 locus regardless of their cytogenetic profile. Interestingly, 15 out of 39 (∼39%) of all CLLs with T12, carry microdeletions of miR-15a/16-1, indicating that, in patients with T12, miR-15a/16-1 are mostly inactivated by microdeletions. In addition, ∼40% of CLL cases bearing T12, 17p−, and 11q− showed unidentified microdeletions of miR-15a/16-1, suggesting that miR-15a/16-1 loss cooperates with such chromosomal alterations in CLL. These data may have clinical relevance for the successful stratification of patients for treatment.
1 citations
TL;DR: This research presents a novel probabilistic procedure that allows for direct measurement of the response of the immune system to earthquake-triggered landsliding.
Abstract: [This corrects the article DOI: 10.1371/journal.pone.0067581.].
1 citations
TL;DR: The first-ever locus-specific analysis of HERV expression in 515 lung adenocarcinoma and 497 lung squamous cell carcinoma patients’ samples from the TCGA repository is presented, believed to help elucidate another layer of dysregulation that occurs in lung cancer involving HERVs, paving the way for identifying novel lung cancer biomarkers.
Abstract: Simple Summary Lung cancer is the leading cause of cancer deaths worldwide. Most lung cancer patients are diagnosed with locally advanced or metastatic diseases, and their prognosis is relatively poor, with 5-year survival rates ranging from 4 to 17%. Consequently, the identification of novel diagnostic lung cancer biomarkers remains crucial. Recently, human endogenous retroviruses (HERVs) have been found to be implicated in cancer development and later employed as novel diagnostic and prognostic cancer biomarkers. In this study, we present the first-ever locus-specific analysis of HERV expression in 515 lung adenocarcinoma (LUAD) and 497 lung squamous cell carcinoma (LUSC) patients’ samples from the TCGA repository. In our study, we identified the differentially expressed HERVs in both TCGA-LUAD and TCGA-LUSC cohorts, we examined their impact on signaling pathways using in silico models, and we described HERVs’ association with overall survival (OS) and relapse-free survival (RFS). Abstract Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide. Among its subtypes, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the most common, accounting for more than 85% of lung cancer diagnoses. Despite the incredible efforts and recent advances in lung cancer treatments, patients affected by this condition still have a poor prognosis. Therefore, novel diagnostic biomarkers are needed. Recently, a class of transposable elements called human endogenous retroviruses (HERVs) has been found to be implicated in cancer development and later employed as novel biomarkers for several tumor types. In this study, we first ever characterized the expression of HERVs at genomic locus-specific resolution in both LUAD and LUSC cohorts available in The Cancer Genome Atlas (TCGA). Precisely, (i) we profiled the expression of HERVs in TCGA-LUAD and TCGA-LUSC cohorts; (ii) we identified the dysregulated HERVs in both lung cancer subtypes; (iii) we evaluated the impact of the dysregulated HERVs on signaling pathways using neural network-based predictions; and (iv) we assessed their association with overall survival (OS) and relapse-free survival (RFS). In conclusion, we believe this study may help elucidate another layer of dysregulation that occurs in lung cancer involving HERVs, paving the way for identifying novel lung cancer biomarkers.
1 citations
1 citations
TL;DR: The microRNA 15a/16-1 cluster on chromosome 13 is commonly lost in chronic lymphocytic leukemia (CLL) and patients with myelodysplastic syndrome (MDS) that transformed into AML as discussed by the authors .