Splicing diversity enhances the molecular classification of pituitary neuroendocrine tumors

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 11, 2025

Pituitary neuroendocrine tumors (PitNETs) are one of the most common intracranial with diverse clinical manifestations. Current pathological classification systems rely primarily on histological hormone staining and transcription factors (TFs) expression. While effective in identifying three major lineages, molecular characteristics based hormones TFs lack sufficient resolution to fully capture complex tumor heterogeneity. Transcriptional diversity by alternative splicing (AS) offered additional insight address this challenge. Here, we perform bulk full-length single-cell RNA sequencing comprehensively investigate AS dysregulation across all PitNET lineages. We reveal pervasive dysregulations that better depict Additionally, delineate fundamental heterogeneity at resolution, confirming findings refining varying among cell types. Notably, effectively distinguish silent corticotroph subtype define a distinct TPIT lineage subtype, which is associated worse outcomes increased abnormalities driven altered ESRP1 In conclusion, our results characterize specific landscape PitNETs, enhancing understanding PitNETs subtyping. pituitary factors. authors analyze revealing subtypes abnormalities.

Язык: Английский

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Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond

Pathology - Research and Practice, Год журнала: 2025, Номер 269, С. 155864 - 155864

Опубликована: Март 1, 2025

Язык: Английский

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Clinically relevant immune subtypes based on alternative splicing landscape of immune-related genes for lung cancer advanced PPPM approach

The EPMA Journal, Год журнала: 2024, Номер 15(2), С. 345 - 373

Опубликована: Май 24, 2024

Язык: Английский

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RBM39 is a potential prognostic biomarker with functional significance in hepatocellular carcinoma

Translational Cancer Research, Год журнала: 2024, Номер 13(4), С. 1606 - 1622

Опубликована: Апрель 1, 2024

RNA-binding motif protein 39 (RBM39) is a well-known involved in tumorigenesis; however, its role hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the RBM39 HCC.

Язык: Английский

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RNA structure in alternative splicing regulation: from mechanism to therapy

Acta Biochimica et Biophysica Sinica, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Alternative splicing is a highly intricate process that plays crucial role in post-transcriptional regulation and significantly expands the functional proteome of limited number coding genes eukaryotes. Its multifactorial, with RNA structure exerting significant impact. Aberrant conformations lead to dysregulation patterns, which directly affects manifestation disease symptoms. In this review, molecular mechanisms secondary structure-mediated are summarized, focus on complex interplay between aberrant phenotypes resulted from defects. This study also explores additional factors reshape structural conformations, enriching our understanding mechanistic network underlying regulation. addition, an emphasis has been placed clinical targeting corrections human diseases. The principal action behind phenomenon described, followed by discussion prospective development strategies pertinent challenges.

Язык: Английский

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Subtype-specific alternative splicing events in breast cancer identified by large-scale data analysis

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 10, 2024

Genome analysis in cancer has focused mainly on elucidating the function and regulatory mechanisms of genes that exhibit differential expression or mutation samples compared to normal samples. Recently, transcriptome revealed abnormal splicing events could contribute pathogenesis. Moreover, variants reportedly generate diverse antigens. Although are expected be potential targets immunotherapy, exploration such their biological significance have not been fully understood. In this study, explore subtype-specific alternative events, we conducted a comprehensive for each breast subtype using large-scale data derived from The Cancer Atlas found patterns. Analyses indicated produce novel immunotherapy against cancer. identified which were by analysis, bring new previously overlooked events.

Язык: Английский

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The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes

Cancers, Год журнала: 2024, Номер 16(11), С. 2123 - 2123

Опубликована: Июнь 1, 2024

Cancer driver genes are either oncogenes or tumour suppressor that classically activated inactivated, respectively, by mutations. Alternative splicing—which produces various mature mRNAs and, eventually, protein variants from a single gene—may also result in driving neoplastic transformation because of the different and often opposed functions genes. The present review analyses alternative splicing events transformation, with an emphasis on their molecular mechanisms. To do this, we collected list 568 gene drivers cancer revised literature to select those involved other as well which its pre-mRNA is subject splicing, result, both cases, producing oncogenic isoform. Thirty-one fall into first category, includes factors components spliceosome regulators. In second namely comprising isoform, 168 were found. Then, grouped them according mechanisms responsible for yielding isoforms, namely, mutations cis splicing-determining elements, causes involving non-mutated changes factors, epigenetic chromatin-related changes. data given substantiate idea aberrant may regulate activation proto-oncogenes inactivation details more than 40

Язык: Английский

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Subtype-specific alternative splicing events in breast cancer identified by large-scale data analysis

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 19, 2024

Genome analysis in cancer has focused mainly on elucidating the function and regulatory mechanisms of genes that exhibit differential expression or mutation samples compared to normal samples. Recently, transcriptome revealed abnormal splicing events could contribute pathogenesis. Moreover, variants reportedly generate diverse antigens. Although are expected be potential targets immunotherapy, exploration such their biological significance have not been fully understood. In this study, explore subtype-specific alternative events, we conducted a comprehensive for each breast subtype using large-scale data derived from The Cancer Atlas found patterns. Analyses indicated produce novel immunotherapy against cancer. identified which were by analysis, bring new previously overlooked events.

Язык: Английский

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Widespread Prevalence of CD19 Exon 5-6 Skipping In Indian Pediatric B-cell Acute Lymphoblastic Leukemia Patients

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the malignant burgeoning of abnormal lymphoblasts. In recent years, use CART therapy which targets CD19 antigen present on surface B-cells, has gained significant attention as a treatment option against aggressive and refractory forms B-ALL. However, loss due to aberrant splicing under pressure been suggested one main factors for emerging resistance. Herein, using RT-PCR based splice assays we examined patterns in 43 primary pediatric B-ALL patient samples spread across various subtypes. We observed that isoform lacking exon 5-6 exists ∼ 55% patients at initial diagnosis stage itself. Using in-silico analysis, identified RNA binding proteins, RC3H1 MBNL1, potential regulators skipping. Furthermore, qRT-PCR analysis revealed MBNL1 are significantly upregulated exhibiting Taken together, first time report existence aberrantly spliced patients, this occurrence could potentially result from dysregulation.

Язык: Английский

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Targeting splicing for hematological malignancies therapy

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Ноя. 11, 2024

Alterations in splicing patterns of leukemic cells have a functional impact and influence most cellular processes since aberrantly spliced isoforms can provide proliferative advantage, enable to evade apoptosis, induce metabolic reprogramming, change cell signaling antitumor immune response, or develop drug resistance. In this Review, we first characterize the general mechanism mRNA processing regulation with focus on role factors, which are commonly mutated blood neoplasms. Next, comprehensive summary current understanding alternative events, confer resistance targeted treatment strategies immunotherapy. We introduce consequences mis-spliced variants (CD19-∆ex2, CD22-∆ex2, CD22-∆ex5-6, CD33-∆ex2, PIK3CD-S, BCR-ABL

Язык: Английский

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