Mechanistic role of DANCR in the choreography of signaling pathways in different cancers: Spotlight on regulation of Wnt/β-catenin and JAK/STAT pathways by oncogenic long non-coding RNA

Farooqı, Ammad Ahmad; Mukhanbetzhanovna, Auyezova Ardak; Yılmaz, Seher; Karasholakova, Lazzat; Ishmuratova, Margarita

doi:10.1016/j.ncrna.2021.01.001

Cited by 8 publications

(7 citation statements)

References 51 publications

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“…A study has shown that NR5A2 is a transcriptional co‐activator of β‐catenin, binding to β‐catenin through its C‐terminal ligand‐binding domain and maintaining the stability of the bond between β‐catenin and the target gene promoter, thereby promoting the transcription of the target gene 20 . Several studies have shown that interference with the NR5A2‐mediated Wnt/β‐catenin pathway using pharmacological agents or via gene regulation can significantly inhibit tumor proliferation, migration, and invasion 21 . In a study of gastric cancer, cancer cell proliferation was inhibited after NR5A2 silencing 22 .…”

Section: Discussionmentioning

confidence: 99%

NR5A2 promotes malignancy progression and mediates the effect of cisplatin in cutaneous squamous cell carcinoma

Ye,

Ya‐xuan,

Shan‐shan

et al. 2024

Immunity Inflam & Disease

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IntroductionNuclear receptor subfamily five group A member two (NR5A2) plays a key role in the development of many tumor types, while it is uncertain in cutaneous squamous cell carcinoma (cSCC). The aim of this work was to determine the role of NR5A2 in cSCC proliferation, and to determine whether NR5A2 mediates the effect of cisplatin in cSCC.MethodsWe performed a systematic study of existing data and conducted a preliminary bioinformatics analysis of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining was performed on cSCC tissues of seven patients to study NR5A2 expression. NR5A2 expression was examined in human keratin‐forming cells (HaCaT) and human cSCC cells (A431, Colo‐16, SCL‐1, SCL‐2, and HSC‐5). Stable A431 and SCL‐2 cell lines consisting of sh‐RNA‐NR5A2 were constructed to detect changes in cell proliferation, cell cycle, apoptosis, and to determine the key proteins in the Wnt/β‐catenin pathway. We also investigated changes in the effects of cisplatin on cSCC cells by CCK‐8, clone formation assay, and Flow apoptosis assay after NR5A2 knockdown.ResultsNR5A2 showed enhanced expression in cSCC tissues than in healthy tissues. Downregulation of NR5A2 in cSCC cells led to the formation of a less malignant phenotype. In contrast, the proliferative capacity of the cSCC cells was enhanced posttreatment with RJW100, an NR5A2 agonist. Additionally, NR5A2 knockdown led to a decrease in the expression level of the proteins in the Wnt/β‐catenin pathway, and this inhibition was reversed by LiCl and recombinant antibody, Wnt3a. Moreover, NR5A2 knockdown resulted in diminished proliferative capacity and increased apoptotic cells after the addition of cisplatin.ConclusionNR5A2 plays a crucial role in the progression of cSCC, and the Wnt/β‐catenin signaling pathway may be involved in the regulation of NR5A2‐mediated cSCC. Knockdown of NR5A2 enhanced both the proliferation inhibiting and apoptosis promoting effects of cisplatin on cSCC.

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Section: Discussionmentioning

confidence: 99%

NR5A2 promotes malignancy progression and mediates the effect of cisplatin in cutaneous squamous cell carcinoma

Ye,

Ya‐xuan,

Shan‐shan

et al. 2024

Immunity Inflam & Disease

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“…16 In tumor cells, when the Wnt/ β-catenin pathway is activated, transcription of target genes were increased by binding directly or indirectly to their promoters, leading to cell proliferation and migration. 17 Thus shown that NR5A2 is a transcriptional co-activator of β-catenin, binding to β-catenin through its Cterminal ligand binding domain and thus maintaining the stability of the bond between β-catenin and the target gene promoter; this in turn promotes the transcription of the target gene. 16 Several studies shown that interference with NR5A2/ β-catenin pathway through pharmacological or gene regulation can significantly inhibit tumor proliferation, migration, and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…16 Several studies shown that interference with NR5A2/ β-catenin pathway through pharmacological or gene regulation can significantly inhibit tumor proliferation, migration, and invasion. 17 In one study of gastric cancer cells, gene silencing activation and attenuated cell proliferation. 18 Another study used exogenous overexpression of microRNA-381 to inhibit the NR5A2/β-catenin signaling pathway, leading to increased apoptosis in colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

NR5A2 promotes the growth and metastasis of cutaneous squamous cell carcinoma A431 cells via the Wnt/β-catenin signaling pathway

Ye,

Ya-xuan,

Shan-shan

et al. 2023

Preprint

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Nuclear receptor subfamily 5 group A member 2 (NR5A2) is known to be a key regulator in the development of a variety of tumor types. However, it is still uncertain how NR5A2 affects cutaneous squamous cell carcinoma (cSCC). The aim of this work, therefore, was to determine the function of NR5A2 in cSCC proliferation, cell cycling, cell migration, and invasion. In this study, based on a systematic study of previous data, we conducted a preliminary exploration of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining for NR5A2 expression was then performed in cSCC tissues and healthy tissues from 7 patients. NR5A2 expression was also examined in human keratin-forming cells (HaCaT) and human cSCC cell lines (A431, Colo-16, SCL-1, and SCL-2). A stable A431 cell line consisting of sh-RNA-NR5A2 was created to detect changes in cell proliferation, cell cycle, clonogenic ability, and the key proteins about the Wnt/β-catenin pathway. The results illustrated that NR5A2 showed enhanced expressed in cSCC tissues than in healthy adjacent tissues and was more robustly expression in Colo-16, A431, SCL-1, and SCL-2 cells versus HaCaT cells. Downregulation of NR5A2 expression in cSCC cells led to a less malignant phenotype. NR5A2 knockdown decreased the expression of proteins in the Wnt/β-catenin, and this inhibition could be reversed by the Wnt signaling pathway agonist LiCl. In conclusion, NR5A2 appears to encourage the development and metastasis of cSCC by Wnt/β-catenin pathway.

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“…Overlap of our DElncRNA and DEPCGs with The Cancer Genome Atlas glioblastoma (TCGA-GBM) patient cohort output yielded two lncRNAs (DANCR and SNHG6) and 222 DEPCGs ( Supplementary file S1 ). DANCR is an oncogenic lncRNA which induces several cancer-promoting effects, such as promotion of angiogenesis and epigenetic silencing of tumor-suppressors; it also regulates cancer-promoting signaling pathways such as the Wnt/β-catenin, JAK/STAT, Notch, and PI3K/AKT pathways (reviewed in [ 93 ]). Due to its pan-oncogenic effect, DANCR has been considered to be a candidate cancer therapeutic target [ 94 , 95 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of RNA-Seq Datasets Identifies Novel Players in Glioblastoma

Sallam

Mysara

Baatout

et al. 2022

Cancers

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Glioblastoma is a devastating grade IV glioma with poor prognosis. Identification of predictive molecular biomarkers of disease progression would substantially contribute to better disease management. In the current study, we performed a meta-analysis of different RNA-seq datasets to identify differentially expressed protein-coding genes (PCGs) and long non-coding RNAs (lncRNAs). This meta-analysis aimed to improve power and reproducibility of the individual studies while identifying overlapping disease-relevant pathways. We supplemented the meta-analysis with small RNA-seq on glioblastoma tissue samples to provide an overall transcriptomic view of glioblastoma. Co-expression correlation of filtered differentially expressed PCGs and lncRNAs identified a functionally relevant sub-cluster containing DANCR and SNHG6, with two novel lncRNAs and two novel PCGs. Small RNA-seq of glioblastoma tissues identified five differentially expressed microRNAs of which three interacted with the functionally relevant sub-cluster. Pathway analysis of this sub-cluster identified several glioblastoma-linked pathways, which were also previously associated with the novel cell death pathway, ferroptosis. In conclusion, the current meta-analysis strengthens evidence of an overarching involvement of ferroptosis in glioblastoma pathogenesis and also suggests some candidates for further analyses.

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Mechanistic role of DANCR in the choreography of signaling pathways in different cancers: Spotlight on regulation of Wnt/β-catenin and JAK/STAT pathways by oncogenic long non-coding RNA

Cited by 8 publications

References 51 publications

NR5A2 promotes malignancy progression and mediates the effect of cisplatin in cutaneous squamous cell carcinoma

NR5A2 promotes malignancy progression and mediates the effect of cisplatin in cutaneous squamous cell carcinoma

NR5A2 promotes the growth and metastasis of cutaneous squamous cell carcinoma A431 cells via the Wnt/β-catenin signaling pathway

Meta-Analysis of RNA-Seq Datasets Identifies Novel Players in Glioblastoma

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