Dysregulation of splicing variants and spliceosome components in breast cancer

Gahete, Manuel D.; Hermán‐Sánchez, Natalia; Fuentes-Fayos, Antonio C; López-Cánovas, Juan L; Luque, Raúl M.

doi:10.1530/erc-22-0019

Cited by 11 publications

(3 citation statements)

References 151 publications

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“…Another notable finding emerging from the transcriptional profiles of adenomas was the enrichment of elements associated with spliceosome observed within three ACs (AC1-3), suggesting a potential role of spliceosome pathway in adrenocortical tumourigenesis, as demonstrated in other benign and malignant tumours 72–74 .…”

Section: Discussionmentioning

confidence: 89%

Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

Altieri

Secener

Sai

et al. 2022

Preprint

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The human adrenal gland is a complex endocrine tissue. Developmental studies on this tissue have been limited to animal models or human foetus. Here, we present a cell atlas analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland development and tumourigenesis. We identified two populations of potential progenitor cells resident within the adrenal cortex: adrenocortical progenitors NR2F2+-ID1+ cells, located within and underneath the capsule, and medullary progenitors SYT1+-CHGA- cells, located in islets in the subcapsular region. Using pseudotime analyses, we provided evidence of the centripetal nature of adrenocortical cell development and of the essential role played by the Wnt/β-catenin pathway in the adrenocortical self-renewal. By comparing transcriptional profiles of cells of normal adrenal glands and adrenocortical adenomas we revealed a high heterogeneity with six adenoma-specific clusters. Overall, our results give insights into adrenal plasticity and mechanisms underlying adrenocortical tumourigenesis.

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Section: Discussionmentioning

confidence: 89%

Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

Altieri

Secener

Sai

et al. 2022

Preprint

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“…It is widely accepted that cancer cells change the expression pattern of proteins in spliceosomes to regulate tumor-related genes expression, leading to the survival and proliferation of cancer cells [ 34 – 36 ]. Consistently, TNBC alter its certain spliceosomal components and splicing factors to meet the need of development and progression, such as enhanced proliferation, inhibited apoptosis, invasion and metastasis, and angiogenesis [ 32 , 37 ]. For example, apoptosis-related gene Bcl-x contains two isoforms Bcl-xL and Bcl-xS.…”

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Polyphyllin D-Treated Triple-Negative Breast Cancer Cells Reveal the Anticancer Mechanisms of Polyphyllin D

Wei,

Mao,

Liu

et al. 2023

Appl Biochem Biotechnol

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Polyphyllin D (PD), one of the important steroid saponins in traditional medicinal herb Paris polyphylla, has been demonstrated to have anticancer activity both in vitro and in vivo. However, the mechanisms through which PD exerts its anticancer effects in triple-negative breast cancer (TNBC) remain unclear. Our study was presented to evaluate the anticancer effect and the potential mechanisms of PD in two TNBC cell lines, BT-549 and MDA-MB-231. Through comprehensively comparing the liquid chromatography-tandem mass spectrometry (LC–MS/MS) data of PD-treated and untreated BT-549 and MDA-MB-231 cells, we found that PD could induce apoptosis of TNBC cells by activating oxidative phosphorylation pathway in BT-549 cells, as well as inhibiting spliceosome function alteration in MDA-MB-231 cells. These results suggested that the mechanisms underlying the pro-apoptotic effect of PD on TNBC may be cell type-specificity-dependent. Moreover, we found that nodal modulator 2/3 (NOMO2/3) were downregulated both in PD-treated BT-549 and MDA-MB-231 cells, suggesting that NOMO2/3 may be the potential target of PD. Verification experiments revealed that PD deceased NOMO2/3 expression at protein level, rather than mRNA level. Whether NOMO2/3 are the upstream modulators of oxidative phosphorylation pathway and spliceosome needs further validation. In conclusion, a comprehensive proteomics study was performed on PD-treated or untreated TNBC cells, revealing the anticancer mechanisms of PD.

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“…Dysregulation of the splicing process and ribosomal modifications are both closely related to tumorigenesis. [76][77][78][79][80] These findings provide insight into the mechanisms underlying the high-risk group of LUAD patients and could potentially lead to the development of targeted therapies to improve prognosis for this group.…”

mentioning

confidence: 94%

Integrative Analysis of Single-Cell and Bulk RNA Sequencing Reveals Prognostic Characteristics of Macrophage Polarization-Related Genes in Lung Adenocarcinoma

Mi,

Zeng,

Chen

et al. 2023

IJGM

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Background Lung adenocarcinoma (LUAD) is a group of cancers with poor prognosis. The combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) can identify important genes involved in cancer development and progression from a broader perspective. Methods The scRNA-seq data and bulk RNA-seq data of LUAD were downloaded from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Analyzing scRNA-seq for core cells in the GSE131907 dataset, and the uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Macrophage polarization-associated subtypes were acquired from the TCGA-LUAD dataset after analysis, followed by further identification of differentially expressed genes (DEGs) in the TCGA-LUAD dataset (normal/LUAD tissue samples, two subtypes). Venn diagrams were utilized to visualize differentially expressed and highly variable macrophage polarization-related genes. Subsequently, a prognostic risk model for LUAD patients was constructed by univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO), and the model was investigated for stability in the external data GSE72094. After analyzing the correlation between the trait genes and significantly mutated genes, the immune infiltration between the high/low-risk groups was then examined. The Monocle package was applied to analyze the pseudo-temporal trajectory analysis of different cell clusters in macrophage clusters. Subsequently, cell clusters of data macrophages were selected as key cell clusters to explore the role of characteristic genes in different cell populations and to identify transcription factors (TFs) that affect signature genes. Finally, qPCR were employed to validate the expression levels of prognosis signature genes in LUAD. Results 424 macrophage highly variable genes, 3920 DEGs, and 9561 DEGs were obtained from macrophage clusters, the macrophage polarization-related subtypes, and normal/LUAD tissue samples, respectively. Twenty-eight differentially expressed and highly mutated MPRGs were obtained. A prognostic risk model with 7 DE-MPRGs (RGS13, ADRB2, DDIT4, MS4A2, ALDH2, CTSH, and PKM) was constructed. This prognostic model still has a good prediction effect in the GSE72094 dataset. ZNF536 and DNAH9 were mutated in the low-risk group, while COL11A1 was mutated in the high-risk group, and they were highly correlated with the characteristic genes. A total of 11 immune cells were significantly different in the high/low-risk groups. Five cell types were again identified in the macrophage cluster, and then NK cells: CD56hiCD62L+ differentiated earlier and were present mainly on 2 branches. While macrophages were present on 2 branches and differentiated later. It was found that the expression levels of BCLAF1 and MAX were higher in cluster 1, which might be the TFs affecting the expression of the characteristic genes. Moreover, qPCR confi...

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Dysregulation of splicing variants and spliceosome components in breast cancer

Cited by 11 publications

References 151 publications

Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

Cell Atlas at Single-Nuclei Resolution of the Adult Human Adrenal Gland and Adrenocortical Adenomas

Proteomics Analysis of Polyphyllin D-Treated Triple-Negative Breast Cancer Cells Reveal the Anticancer Mechanisms of Polyphyllin D

Integrative Analysis of Single-Cell and Bulk RNA Sequencing Reveals Prognostic Characteristics of Macrophage Polarization-Related Genes in Lung Adenocarcinoma

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