Advances in the Relationship Between Regulator of Ribosome Synthesis 1 (RRS1) and Diseases

Hua, Yanan; Song, Jinping; Peng, Cuixiu; Wang, Runze; Zhang, Jinyu; Zhang, Zheng; Li, Ning; Hou, Lin

doi:10.3389/fcell.2021.620925

Cited by 12 publications

(12 citation statements)

References 77 publications

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“…Expression of a core mediator of ribosomal assembly RRS1 was also increased at the protein level (Fig. 2g) (Hua et al, 2021). This was unexpected, since ribosome biogenesis is generally suppressed under stress (Lindstrom et al, 2022; Ni and Buszczak, 2023; Szaflarski et al, 2022), and LONP2-depletion in COS-7 cells resulted in strong reduction in protein synthesis ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism

Yamashita

Ignatenko

Nguyen

et al. 2023

Preprint

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Peroxisomes play a central role in tuning metabolic and signaling programs in a tissue- and cell type-specific manner. However, the mechanisms by which the status of peroxisomes is communicated and integrated into cellular signaling pathways is not yet understood. Herein, we report the cellular responses to acute peroxisomal proteotoxic stress upon silencing the peroxisomal protease/chaperone LONP2. Depletion of LONP2 triggered accumulation of its substrates, alterations in peroxisome size and numbers, and luminal protein import failure. Gene expression changes and lipidomic analysis revealed striking cell specific differences in the response to siLONP2. Specific to COS-7 cells was a strong activation of the integrated stress response (ISR) and upregulation of ribosomal biogenesis gene expression levels. Common changes between COS-7 and U2OS cell lines included repression of the retinoic acid signaling pathway, and upregulation of sphingolipids. Cholesterol accumulated in the endomembrane compartments in both cell lines, consistent with evidence that peroxisomes are required for cholesterol flux out of late endosomes. These unexpected consequences of peroxisomal stress provide an important insight for our understanding of the tissue-specific responses seen in peroxisomal disorders.

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Section: Resultsmentioning

confidence: 99%

Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism

Yamashita

Ignatenko

Nguyen

et al. 2023

Preprint

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“…Also, the downregulation of lncRNA SET-binding factor 2-antisense RNA1 can upregulate miR-143 and inhibit RRS1 and ultimately restrict the progression of breast cancer ( 50 ). In addition, dysregulation of RRS1 is involved in the development of several malignancies and the progression of various tumors, including papillary thyroid carcinoma, retinoblastoma, and neuroblastoma ( 51 – 54 ). These studies confirm the key role of RRS1 in tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics and machine-learning screening for immune-related genes in diagnosing non-alcoholic fatty liver disease with ischemic stroke and RRS1 pan-cancer analysis

Bao

Zhang

et al. 2023

Front. Immunol.

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BackgroundThe occurrence of ischemic stroke (IS) is associated with nonalcoholic fatty liver disease (NAFLD). The cancer burden of NAFLD complicated by IS also warrants attention. This study aimed to identify candidate immune biomarkers linked to NAFLD and IS and analyze their association with cancer.MethodsTwo of each of the NAFLD and IS datasets were downloaded, differentially expressed genes (DEGs) were identified, and module genes were screened via weighted gene coexpression network analysis (WGCNA). Subsequently, utilizing machine learning (least absolute shrinkage and selection operator regression, random forest and support vector machine-recursive feature elimination) and immune cell infiltration analysis, immune-related candidate biomarkers for NAFLD with IS were determined. Simultaneously, a nomogram was established, the diagnostic efficacy was assessed, and the role of candidate biomarkers in cancer was ascertained through pan-cancer analyses.ResultsIn this study, 117 and 98 DEGs were identified from the combined NAFLD and IS datasets, respectively, and 279 genes were obtained from the most significant modules of NAFLD. NAFLD module genes and IS DEGs were intersected to obtain nine genes, which were enriched in the inflammatory response and immune regulation. After overlapping the results of the three machine learning algorithms, six candidate genes were obtained, based on which a nomogram was constructed. The calibration curve demonstrated good accuracy, and the candidate genes had high diagnostic values. The genes were found to be related to the immune dysregulation of stroke, and RRS1 was strongly associated with the prognosis, immune cell infiltration, microsatellite instability (MSI), and tumor mutation burden (TMB).ConclusionSix common candidate immune-related genes (PTGS2, FCGR1A, MMP9, VNN3, S100A12, and RRS1) of NAFLD and IS were identified, and a nomogram for diagnosing NAFLD with IS was established. RRS1 may serve as a candidate gene for predicting the prognosis of patients with cancer who have NAFLD complicated by IS, which could aid in their diagnosis and treatment.

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“…RRS1 (regulator of ribosome synthesis 1) is principally localized in the nucleolus and endoplasmic reticulum [ 55 ]. Recent studies regarded RRS1 as a tumor promotor and concluded that overexpression of RRS1 could facilitate the growth and metastasis of various tumors [ 56 ]. In the molecular mechanism, RRS1 participates in ribosome biosynthesis and mainly influences chromosomal and telomeric arrangement during the cell cycle [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Constructing a seventeen-gene signature model for non-obstructive azoospermia based on integrated transcriptome analyses and WGCNA

Chen

Yuan

et al. 2023

Reprod Biol Endocrinol

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Background Non-obstructive azoospermia (NOA) affects approximately 1% of the male population worldwide. The underlying mechanism and gene transcription remain unclear. This study aims to explore the potential pathogenesis for the detection and management of NOA. Methods Based on four microarray datasets from the Gene Expression Omnibus database, integrated analysis and weighted correlation network analysis (WGCNA) were used to obtain the intersected common differentially expressed genes (DESs). Differential signaling pathways were identified via GO and GSVA-KEGG analyses. We constructed a seventeen-gene signature model using least absolute shrinkage and selection operation (LASSO) regression, and validated its efficacy in another two GEO datasets. Three patients with NOA and three patients with obstructive azoospermia were recruited. The mRNA levels of seven key genes were measured in testicular samples, and the gene expression profile was evaluated in the Human Protein Atlas (HPA) database. Results In total, 388 upregulated and 795 downregulated common DEGs were identified between the NOA and control groups. ATPase activity, tubulin binding, microtubule binding, and metabolism- and immune-associated signaling pathways were significantly enriched. A seventeen-gene signature predictive model was constructed, and receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values were 1.000 (training group), 0.901 (testing group), and 0.940 (validation set). The AUCs of seven key genes (REC8, CPS1, DHX57, RRS1, GSTA4, SI, and COX7B) were all > 0.8 in both the testing group and the validation set. The qRT-PCR results showed that consistent with the sequencing data, the mRNA levels of RRS1, GSTA4, and COX7B were upregulated, while CPS1, DHX57, and SI were downregulated in NOA. Four genes (CPS1, DHX57, RRS1, and SI) showed significant differences. Expression data from the HPA database showed the localization characteristics and trajectories of seven key genes in spermatogenic cells, Sertoli cells, and Leydig cells. Conclusions Our findings suggest a novel seventeen-gene signature model with a favorable predictive power, and identify seven key genes with potential as NOA-associated marker genes. Our study provides a new perspective for exploring the underlying pathological mechanism in male infertility.

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Advances in the Relationship Between Regulator of Ribosome Synthesis 1 (RRS1) and Diseases

Cited by 12 publications

References 77 publications

Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism

Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism

Integrated bioinformatics and machine-learning screening for immune-related genes in diagnosing non-alcoholic fatty liver disease with ischemic stroke and RRS1 pan-cancer analysis

Constructing a seventeen-gene signature model for non-obstructive azoospermia based on integrated transcriptome analyses and WGCNA

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