LncRNA SNHG6 promotes glycolysis reprogramming in hepatocellular carcinoma by stabilizing the BOP1 protein

Chen, Kai; Wang, Xi; Wei, Bowen; Sun, Rongcun; Wu, Chunlin; Yang, Hongji

doi:10.1080/19768354.2022.2134206

Cited by 11 publications

(6 citation statements)

References 42 publications

(42 reference statements)

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“…BOP1 (Block of proliferation 1) was up-regulation in HCC and promoted epithelial-to-mesenchymal transition [33]. A recent report states that the BOP1 protein is stabilized by long non-coding RNA SNHG6, leading to glycolytic reprogramming in HCC [34]. The IPO7 (importin-7) belongs to the importin-β family and mediates the nuclear import of cargo [35].…”

Section: Discussionmentioning

confidence: 99%

Personalized Therapies in Hepatocellular Carcinoma: Insights from a Disulfidptosis-Related Signature

Wan,

Xu,

Zhou

et al. 2024

Preprint

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Hepatocellular carcinoma (HCC) is the predominant pathological type of liver cancer with an unfavorable prognosis. Disulfidptosis is the newest cell death form and plays a vital role in tumorigenesis. However, the role of disulfidptosis-related genes (DRGs) in HCC remains unknown. The RNA-seq and clinical data of HCC patients were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Based on DRGs in TCGA cohort, the predictive model was established via regression analysis of the least absolute shrinkage and selection operator (LASSO) and subsequently validated using ICGC cohort. Moreover, we investigated the relationship between predictive model and clinical features, somatic mutations, molecular mechanism, immune microenvironment and drug response. This study created an eight-gene signature. Here, we noticed a higher level of those eight genes in HCC patients in both RNA and protein levels. The patients in the high-risk group had a poor prognosis. It was found the predictive model was an independent prognostic factor by Multivariate Cox analyses. Pathways involved in cancer, cell membrane, and metabolism was significantly enriched. In addition, tumor mutation burden (TMB) and immune checkpoint genes expression were higher in the high-risk group. Furthermore, the high-risk group was more sensitive to immunotherapy and some targeted therapy. We comprehensively and systematically identified a new disulfidptosis-related signature, which could serve as a valuable tool for predicting prognosis, immune cell infiltration and therapy response of HCC patients. Thus, these discoveries could have potentially clinical value in directing personalized therapies in the future.

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Section: Discussionmentioning

confidence: 99%

Personalized Therapies in Hepatocellular Carcinoma: Insights from a Disulfidptosis-Related Signature

Wan,

Xu,

Zhou

et al. 2024

Preprint

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“…In addition to protein-coding genes, long-noncoding RNA (lncRNAs) are RNA molecules with a length of over 200 nt that possess various functions in regulating gene transcription, epigenetic regulation, and cell proliferation and differentiation (Esteller 2011 ; Chen et al 2022 ). Recently, several studies have investigated the roles of lncRNAs in the immunity of fish (Wang et al 2018 ; Leiva et al 2020 ; Zheng et al 2021a ; Haridevamuthu et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of TRAF6 -knockout on gene expression and lncRNA expression in Epithelioma papulosum cyprini (EPC) cells

Abdellaoui,

Kim,

Kim

2023

Animal Cells and Systems

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TRAF6 is a key immune gene that plays a significant role in toll-like receptor signal transduction and activates downstream immune genes involved in antiviral immunity in fish. To explore the role of TRAF6 in Epithelioma papulosum cyprini (EPC) cells, we knocked out the TRAF6 gene using the Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 (CRISPR-Cas9) technique and then analyzed the transcriptomes of the knockout cells. In this study, we identified that 232 transcripts were differentially expressed in naive cells. Using the pipeline, we identified 381 novel lncRNAs in EPC cells, 23 of which were differentially expressed. Gene Ontology enrichment analysis demonstrated that differentially expressed genes (DEG) are implicated in various immune processes, such as neutrophil chemotaxis and mitogen-activated protein kinase binding. In addition, the KEGG pathway analysis revealed enrichment in immune-related pathways (Interleukin-17 signaling pathway, cytokine-cytokine receptor interaction, and TNF signaling pathway). Furthermore, the target genes of the differentially expressed lncRNAs were implicated in the negative regulation of interleukin-6 and tumor necrosis factor production. These results indicate that lncRNAs and protein-coding genes participate in the regulation of immune and metabolic processes in fish.

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“…SNHG6 is a lncRNA with a known impact in several cancer types [68][69][70][71][72][73][74], and is significantly associated with a poor prognosis in acute myeloid leukemia (Fig. 4a).…”

Section: Snhg6 Regulates Hematopoiesis In K562 Cellsmentioning

confidence: 99%

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

Hazan,

Amador,

Ali-Nasser

et al. 2024

J Biomed Sci

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Background Long non-coding RNAs (lncRNAs) are pivotal players in cellular processes, and their unique cell-type specific expression patterns render them attractive biomarkers and therapeutic targets. Yet, the functional roles of most lncRNAs remain enigmatic. To address the need to identify new druggable lncRNAs, we developed a comprehensive approach integrating transcription factor binding data with other genetic features to generate a machine learning model, which we have called INFLAMeR (Identifying Novel Functional LncRNAs with Advanced Machine Learning Resources). Methods INFLAMeR was trained on high-throughput CRISPR interference (CRISPRi) screens across seven cell lines, and the algorithm was based on 71 genetic features. To validate the predictions, we selected candidate lncRNAs in the human K562 leukemia cell line and determined the impact of their knockdown (KD) on cell proliferation and chemotherapeutic drug response. We further performed transcriptomic analysis for candidate genes. Based on these findings, we assessed the lncRNA small nucleolar RNA host gene 6 (SNHG6) for its role in myeloid differentiation. Finally, we established a mouse K562 leukemia xenograft model to determine whether SNHG6 KD attenuates tumor growth in vivo. Results The INFLAMeR model successfully reconstituted CRISPRi screening data and predicted functional lncRNAs that were previously overlooked. Intensive cell-based and transcriptomic validation of nearly fifty genes in K562 revealed cell type-specific functionality for 85% of the predicted lncRNAs. In this respect, our cell-based and transcriptomic analyses predicted a role for SNHG6 in hematopoiesis and leukemia. Consistent with its predicted role in hematopoietic differentiation, SNHG6 transcription is regulated by hematopoiesis-associated transcription factors. SNHG6 KD reduced the proliferation of leukemia cells and sensitized them to differentiation. Treatment of K562 leukemic cells with hemin and PMA, respectively, demonstrated that SNHG6 inhibits red blood cell differentiation but strongly promotes megakaryocyte differentiation. Using a xenograft mouse model, we demonstrate that SNHG6 KD attenuated tumor growth in vivo. Conclusions Our approach not only improved the identification and characterization of functional lncRNAs through genomic approaches in a cell type-specific manner, but also identified new lncRNAs with roles in hematopoiesis and leukemia. Such approaches can be readily applied to identify novel targets for precision medicine.

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LncRNA SNHG6 promotes glycolysis reprogramming in hepatocellular carcinoma by stabilizing the BOP1 protein

Cited by 11 publications

References 42 publications

Personalized Therapies in Hepatocellular Carcinoma: Insights from a Disulfidptosis-Related Signature

Personalized Therapies in Hepatocellular Carcinoma: Insights from a Disulfidptosis-Related Signature

Effect of TRAF6 -knockout on gene expression and lncRNA expression in Epithelioma papulosum cyprini (EPC) cells

Integration of transcription regulation and functional genomic data reveals lncRNA SNHG6’s role in hematopoietic differentiation and leukemia

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