Small nucleolar RNA host gene 8: A rising star in the targets for cancer therapy

Yuan, Xin; Yan, Yichao; Xue, Miaomiao

doi:10.1016/j.biopha.2021.111622

Cited by 12 publications

(9 citation statements)

References 55 publications

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“…All findings suggested that SNHG15 was promising as a biomarker and therapeutic target for cancer patients. Similarly, SNHG8 was considered to be an oncogenic factor and was upregulated in various types of cancer (Yuan et al, 2021), such as gastric cancer, melanoma, nasopharyngeal cancer, and esophageal cancer (Shan et al, 2022b;Luan et al, 2022;Wu et al, 2022;Zhu et al, 2022). LINC00471 was an essential member of the prognostic model of childhood acute myeloid leukemia and esophageal squamous cell carcinoma (Zhang et al, 2019a;Yu et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma

Liu

Chang

et al. 2022

Front. Genet.

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Background: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated cell death differs from previously known death mechanisms (apoptosis, ferroptosis, and necroptosis) and is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254–1261). Studies also suggested that targeting cuproptosis may be a novel therapeutic strategy for cancer therapy. In ccRCC, both cuproptosis and lncRNA were critical, but the mechanisms were not fully understood. The aim of our study was to construct a prognostic profile based on cuproptosis-associated lncRNAs to predict the prognosis of ccRCC and to study the immune profile of clear cell renal cell carcinoma (ccRCC).Methods: We downloaded the transcriptional profile and clinical information of ccRCC from The Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-associated lncRNAs and to construct a risk prognostic model. In addition, the predictive performance of the model was validated and recognized by an integrated approach. We then also constructed a nomogram to predict the prognosis of ccRCC patients. Differences in biological function were investigated by GO, KEGG, and immunoassay. Immunotherapy response was measured using tumor mutational burden (TMB) and tumor immune dysfunction and rejection (TIDE) scores.Results: We constructed a panel of 10 cuproptosis-associated lncRNAs (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, and MINCR) to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. The cuproptosis-associated lncRNA model had higher diagnostic efficiency compared to other clinical features. The analysis of Immune cell infiltration and ssGSEA further confirmed that predictive features were significantly associated with the immune status of ccRCC patients. Notably, the superimposed effect of patients in the high-risk group and high TMB resulted in shorter survival. In addition, the higher TIDE scores in the high-risk group suggested a poorer outcome for immune checkpoint blockade response in these patients.Conclusion: The ten cuproptosis-related risk profiles for lncRNA may help assess the prognosis and molecular profile of ccRCC patients and improve treatment options, which can be further applied in the clinic.

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Section: Discussionmentioning

confidence: 99%

Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma

Liu

Chang

et al. 2022

Front. Genet.

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“…Small nucleolar RNA host genes (SNHGs) are a group of lncRNAs that contain introns and exons in their sequences and generate small nucleolar RNAs through alternative splicing. SNHG8 is a newly identified type of small nucleolus host RNA belonging to the lincRNA family, located on chromosome 4q26 (Williams and Farzaneh 2012; Yuan, Yan, and Xue 2021). SNHG8 is expressed by most cell types in the brain including neurons, oligodendrocytes, microglia, and astrocytes (Y.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNASNHG8drives stress granule formation in tauopathies

Bhagat

Minaya

Renganathan

et al. 2023

Preprint

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Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in theMAPTgene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream ofMAPTmutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying aMAPTp.P301L, IVS10+16, or p.R406W mutation, and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of theMAPTmutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the threeMAPTmutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs,SNHG8was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer’s disease brains. We show thatSNHG8interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tauin vitrois sufficient to reduceSNHG8expression and induce stress granule formation. RescuingSNHG8expression leads to reduced stress granule formation and reduced TIA1 levels, suggesting that dysregulation of this non-coding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies.

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“…In this study, SNHG8 dramatically decreased during OTM, both in vivo and in vitro. SNHG8 is a tumor-associated lncRNA upregulated in various tumor types, increasing the proliferation, migration, invasion, and metastasis of cancer cells [ 34 ]. In non-tumor diseases, upregulated SNHG8 serves as a competitive endogenous RNA by sponging miR‐425‐5p, and inhibits the SIRT1/NF‐κB signaling pathway to attenuate the ischemia-induced microglial inflammatory response [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment

et al. 2022

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Background A series of biochemical responses, including hypoxia and aseptic inflammation, occur in periodontal ligament cells (PDLCs) during periodontal tissue remodeling of orthodontic tooth movement (OTM). However, the role of long non-coding RNA (lncRNA) in these responses is still largely unknown. We investigated the role of the lncRNA SNHG8 in hypoxic and inflammatory responses during OTM and explored the underlying mechanisms. Methods The expression pattern of SNHG8, and hypoxic and inflammatory responses under compressive force were analyzed by qRT-PCR, immunohistochemistry, and western blotting, in vivo and in vitro. The effect of overexpression or knockdown of SNHG8 on the nuclear factor-kappaB (NF-κB) pathway was evaluated. RNA sequencing was performed for mechanistic analysis. The interaction between SNHG8 and hypoxia-inducible factor (HIF)-1α was studied using catRAPID, RNA immunoprecipitation, and RNA pulldown assays. The effect of the SNHG8–HIF-1α interaction on the NF-κB pathway was determined by western blotting. Results The NF-κB pathway was activated, and HIF-1α release was stabilized, in PDLCs under compressive force as well as in OTM model rats. The SNHG8 level markedly decreased both in vivo and in vitro. Overexpression of SNHG8 decreased the expression levels of inflammatory cytokines, the phosphorylation of p65, and the degradation of IκBα in PDLCs, whereas knockdown of SNHG8 reversed these effects. Mechanically, RNA sequencing showed that differentially expressed genes were enriched in cellular response to hypoxia after SNHG8 overexpression. SNHG8 binds to HIF-1α, thus preventing HIF-1 from activating downstream genes, including those related to the NF-κB pathway. Conclusion SNHG8 binds to HIF-1α. During OTM, the expression of SNHG8 dramatically decreased, releasing free functional HIF-1α and activating the downstream NF-κB pathway. These data suggest a novel lncRNA-regulated mechanism during periodontal tissue remodeling in OTM.

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Small nucleolar RNA host gene 8: A rising star in the targets for cancer therapy

Cited by 12 publications

References 55 publications

Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma

Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma

Long non-coding RNASNHG8drives stress granule formation in tauopathies

A reduced level of the long non-coding RNA SNHG8 activates the NF-kappaB pathway by releasing functional HIF-1alpha in a hypoxic inflammatory microenvironment

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