Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer

Brahim, Sonia; Negulescu, Ana-Maria; Geneste, Clara; Schøtt, Thomas; Lin, Shuheng; Morel, Louis-Oscar; Rama, Nicolas; Gadot, Nicolas; Treilleux, Isabelle; Mehlen, Patrick; Meurette, Olivier

doi:10.1038/s41419-023-05674-7

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…Further, it was reported that miR-218-5p can simultaneously bind hsa_circ_0058124 and Numb, a significant Notch signaling suppressor. Notch signaling, in a multitude of cancer types, functions to prevent initiation and propagation of tumorigenesis and serves as an extensive cell cycle regulator via Mybl2 [71]. The expression level of Numb was detected in PTC patient samples via qRT-PCR and found to be significantly upregulated along with hsa_circ_0058124, confirming a ceRNA axis of regulation between these three transcripts.…”

Section: Role Of Hsa_circ_0058124 In Thyroid Cancermentioning

confidence: 85%

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential

DeSouza,

Nielsen,

Jarboe

et al. 2024

Biomolecules

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Circular RNAs (circRNAs) are stable, enclosed, non-coding RNA molecules with dynamic regulatory propensity. Their biogenesis involves a back-splicing process, forming a highly stable and operational RNA molecule. Dysregulated circRNA expression can drive carcinogenic and tumorigenic transformation through the orchestration of epigenetic modifications via extensive RNA and protein-binding domains. These multi-ranged functional capabilities have unveiled extensive identification of previously unknown molecular and cellular patterns of cancer cells. Reliable circRNA expression patterns can aid in early disease detection and provide criteria for genome-specific personalized medicine. Studies described in this review have revealed the novelty of circRNAs and their biological ss as prognostic and diagnostic biomarkers.

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Section: Role Of Hsa_circ_0058124 In Thyroid Cancermentioning

confidence: 85%

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential

DeSouza,

Nielsen,

Jarboe

et al. 2024

Biomolecules

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“…Dysregulation of Notch3 has been associated with numerous cancers [ 44 , 45 ], impacting tumor aggressiveness, maintenance, and resistance to chemotherapy [ 46 – 48 ]. In addition, studies found that NOTCH3 can have a role in orchestrating antitumoral activity by inducing the expression of PD-1 [ 49 , 50 ].…”

Section: Case Presentation and Discussionmentioning

confidence: 99%

Molecular profiling of a bladder cancer with very high tumour mutational burden

Scimeca,

Bischof,

Bonfiglio

et al. 2024

Cell Death Discov.

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The increasing incidence of urothelial bladder cancer is a notable global concern, as evidenced by the epidemiological data in terms of frequency, distribution, as well as mortality rates. Although numerous molecular alterations have been linked to the occurrence and progression of bladder cancer, currently there is a limited knowledge on the molecular signature able of accurately predicting clinical outcomes. In this report, we present a case of a pT3b high-grade infiltrating urothelial carcinoma with areas of squamous differentiation characterized by very high tumor mutational burden (TMB), with up-regulations of immune checkpoints. The high TMB, along with elevated expressions of PD-L1, PD-L2, and PD1, underscores the rationale for developing a personalized immunotherapy focused on the use of immune-checkpoint inhibitors. Additionally, molecular analysis revealed somatic mutations in several other cancer-related genes, including TP53, TP63 and NOTCH3. Mutations of TP53 and TP63 genes provide mechanistic insights on the molecular mechanisms underlying disease development and progression. Notably, the above-mentioned mutations and the elevated hypoxia score make the targeting of p53 and/or hypoxia related pathways a plausible personalized medicine option for this bladder cancer, particularly in combination with immunotherapy. Our data suggest a requirement for molecular profiling in bladder cancer to possibly select appropriate immune-checkpoint therapy.

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A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer

Wu,

Liu,

Wang

et al. 2024

Environmental Toxicology

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BackgroundThe metabolism of abnormal bile acids (BAs) is implicated in the initiation and development of gastrointestinal (GI) cancer. However, there was a lack of research on the molecular mechanisms of BAs metabolism in GI.MethodsGenes involved in BAs metabolism were excavated from public databases of The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database, and Molecular Signatures Database (MSigDB). ConsensusClusterPlus was used to classify molecular subtypes for GI. To develop a RiskScore model for predicting GI prognosis, univariate Cox analysis was performed on the genes in protein–protein interaction (PPI) network, followed by using Lasso regression and stepwise regression to refine the model and to determine the key prognostic genes. Tumor immune microenvironment in GI patients from different risk groups was assessed using the ESTIMATE algorithm and enrichment analysis. Reverse transcription–quantitative real‐time PCR (RT‐qPCR), Transwell assay, and wound healing assay were carried out to validate the expression and functions of the model genes.ResultsThis study defined three molecular subtypes (C1, C2, and C3). Specifically, C1 had the best prognosis, while C3 had the worst prognosis with high immune checkpoint gene expression levels and TIDE scores. We selected nine key genes (AXIN2, ATOH1, CHST13, PNMA2, GYG2, MAGEA3, SNCG, HEYL, and RASSF10) that significantly affected the prognosis of GI and used them to develop a RiskScore model accordingly. Combining the verification results from a nomogram, the prediction of the model was proven to be accurate. The high RiskScore group was significantly enriched in tumor and immune‐related pathways. Compared with normal gastric mucosal epithelial cells, the mRNA levels of the nine genes were differential in the gastric cancer cells. Inhibition of PNMA2 suppressed migration and invasion of the cancer cells.ConclusionWe distinguished three GI molecular subtypes with different prognosis based on the genes related to BAs metabolism and developed a RiskScore model, contributing to the diagnosis and treatment of patients with GI.

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Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer

Cited by 5 publications

References 35 publications

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential

Dysregulated Expression Patterns of Circular RNAs in Cancer: Uncovering Molecular Mechanisms and Biomarker Potential

Molecular profiling of a bladder cancer with very high tumour mutational burden

A prognostic model established using bile acid genes to predict the immunity and survival of patients with gastrointestinal cancer

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