Biology subjects

Croce, C. M.

Publications and source records attributed to Croce, C. M..

4 recordsLinked to original sources

bioRxiv2025

A tumor suppressor role of the miR-15b/16-2 cluster in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy arising from the neoplastic transformation of immature T cells during their development in the thymus. Deciphering the developmental programs whose dysregulation leads to T-ALL pathogenesis is critical for the development of novel targeted therapies, which remain an urgent unmet need for the treatment of this disease. MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of numerous physiological processes and cancer. However, the specific role of miRNAs in human T-cell development and T-ALL pathogenesis remains largely unexplored. In this study, we comprehensively evaluated miRNA expression profiles across human T-cell development by microarray analysis and identified a dynamic expression pattern of miR-16-2, which is upregulated across early pre-T cell proliferative stages up to the resting stage of immature thymocytes immediately preceding TCR{beta} expression, and decreased thereafter. We confirmed the coordinated regulation of miR-15b expression, consistent with the reported clustered genomic location of both miRNAs. Notably, functional studies identified the miR-15b/16-2 cluster as a negative regulator of early thymocyte proliferation, and showed that overexpression of miR-15b/16-2 in T-ALL cells impaired leukemic growth in vitro and tumor progression in patient-derived xenotransplantation assays. Mechanistically, miR-15b/16-2 expression represses the genes encoding BCL-2 and CYCLIN D3, leading to T-ALL apoptosis and cell cycle dysregulation, with an accumulation of G0-phase cells and a defective transition to the G2/M phase. Overall, these findings support a novel function for miR-15b/16-2 as tumor suppressors in T-ALL, highlighting their role as promising targets for T-ALL therapy. KEY POINTSO_LImiR-15b/16-2 overexpression impairs the proliferation of human thymic progenitors leading to defective T-cell production. C_LIO_LImiR-15b/16-2 represses BCL-2 and CYCLIN D3 expression and impairs tumor progression in human T-ALL, revealing its role as tumor suppressor. C_LI

immunology↗

bioRxiv2024

miR-155 expression and function in leukemic stem cells

It has been reported that elevated levels of miR-155 have been reported in patients with Acute Myeloid Leukemia (AML) bearing FLT3-ITD mutations and is independent of FLT3-ITD signaling. However, it is unclear how miR-155 is expressed in leukemic stem cells (LCS) and whether miR-155 has any role regulating LSC functions. In this manuscript, we defined the expression of miR-155 in clearly defined LCSs population and showed that miR-155 is regulating self-renewal and quiescence of LSCs.

cancer biology↗

bioRxiv2021

A concurrent canonical and modified miRNAome pan-cancer study on TCGA and TARGET cohorts leads to an enhanced resolution in cancer

MiRNA Epitranscriptomics has placed a new layer of complexity in the cancer field. Despite the fast-growing interest in miRNA editing and shifted miRNA isoforms, a simultaneous study of both modifications in cancer is still missing. Here, we concurrently profiled multiple miRNA modifications, including A-to-I RNA editing and shifted miRNA isoforms, in >13K adult and pediatric tumor samples across 38 distinct cancer cohorts from The Cancer Genome Atlas and The Therapeutically Applicable Research to Generate Effective Treatments datasets. We investigated the differences among canonical miRNAs and the wider miRNAome in terms of expression, clustering, dysregulation, and prognostic standpoint. The combination of canonical miRNAs/miRNA isoforms boosted the quality of clustering results, outlining unique cohorts clinical-pathological features. We described modified miRNAs showing opposite dysregulation with respect to their canonical counterparts in cancer, potentially impacting their targetome and function. The abundance of expressed miRNA isoforms directly impacted the activation/deactivation of critical carcinogenesis pathways. Finally, we experimentally validated unique targeting for a shifted and edited miRNA isoform. Our findings outlined once more the importance of going beyond the well-established paradigm of one-mature-miRNA per miRNA arm to elucidate novel mechanisms related to cancer progression.

cancer biology↗

bioRxiv2020

MiREDiBase: a manually curated database of editing events in microRNAs

MicroRNAs (miRNAs) are regulatory small non-coding RNAs that function as translational repressors. MiRNAs are involved in most cellular processes, and their expression and function are presided by several factors. Amongst, miRNA editing is an epitranscriptional modification that alters the original nucleotide sequence of selected miRNAs, possibly influencing their biogenesis and target-binding ability. A-to-I and C-to-U RNA editing are recognized as the canonical types, with the A-to-I type being the predominant one. Albeit some bioinformatics resources have been implemented to collect RNA editing data, it still lacks a comprehensive resource explicitly dedicated to miRNA editing. Here, we present MiREDiBase, a manually curated catalog of editing events in miRNAs. The current version includes 3,059 unique validated and putative editing sites from 626 pre-miRNAs in humans and three primates. Editing events in mature human miRNAs are supplied with miRNA-target predictions and enrichment analysis, while minimum free energy structures are inferred for edited pre-miRNAs. MiREDiBase represents a valuable tool for cell biology and biomedical research and will be continuously updated and expanded at https://ncrnaome.osumc.edu/miredibase.

bioinformatics↗