Role of UTX Histone Demethylase in Regulation of MGMT, TRA2A, U2AF1, and RPS6KA2 Genes in Prostate Cancer Cell Lines

Khoufaf, Fatma Zohra Houfaf; Sánchez, Alcides Antúnez; Idrissou, Mouhamed; Boisnier, Tiphanie; Penault‐Llorca, Frédérique; Bignon, Yves‐Jean; Guy, Laurent; Bernard‐Gallon, Dominique

doi:10.1089/omi.2020.0183

Cited by 2 publications

(2 citation statements)

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“…RPS6KA2 is the member of RPS6K family ( 12 – 15 ). Different from other RPS6Ks, RPS6KA2 has dual catalytic domains ( 16 ). The first domain is homologous to the cyclic AMP kinase family whereas the second to the phosphorylase kinase family.…”

Section: Introductionmentioning

confidence: 99%

ncRNAs mediated RPS6KA2 inhibits ovarian cancer proliferation via p38/MAPK signaling pathway

Ding

Gong

et al. 2023

Front. Oncol.

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BackgroundOvarian cancer is the most lethal gynecology malignancy in the world, therefore, research on the molecular biological mechanism of ovarian cancer tumorigenesis and progression has received widespread attention.MethodsWe identified RPS6KA2 as the prognosis-related gene of ovarian cancer from TCGA, GSE26712 and GSE26193 database via bioinformatic analysis. qRT-PCR and western blot detected the differential expression of RPS6KA2 in normal ovaries and ovarian cancer tissues. The biological functions of RPS6KA2 were verified by in vitro and in vivo. GSEA analysis was used to select candidate signaling pathway of RPS6KA2 which was further verified by western blot. The possible binding sites of RPS6KA2 with miRNAs and circRNAs were predicted by bioinformatics analysis, and then a circRNA-miRNA-mRNA interaction network was constructed.ResultsWe found the expression of RPS6KA2 was down-regulated in ovarian cancer tissues. Overexpression of RPS6KA2 could suppress cell proliferation, whereas knockdown of RPS6KA2 had the opposite effects on proliferation. GSEA analysis showed that the MARK signaling pathway was closely associated with RPS6KA2. Bioinformatics analysis and dual-luciferase reporter assay showed that RPS6KA2 was regulated with miR-19a-3p, miR-106a-5p and miR-519d-3p. Further analysis showed that circFAM169A was the common ceRNA of miR-19a-3p, miR-106a-5p and miR-519d-3p. Dual-luciferase reporter assay showed the relationship of circFAM169A and miR-106a-5p and miR-519d-3p. After network analysis, one circRNA-miRNA-mRNA axis (circFAM169A/miR-106a-5p, miR-519d-3p/RPS6KA2) was identified.ConclusionsWe demonstrated that circFAM169A/miR-106a-5p, miR-519d-3p mediated low expression of RPS6KA2 could affect the proliferation of ovarian cancer cells via p38/MAPK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

ncRNAs mediated RPS6KA2 inhibits ovarian cancer proliferation via p38/MAPK signaling pathway

Ding

Gong

et al. 2023

Front. Oncol.

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“…TRA2A is upregulated in glioma cells and drives epithelial-mesenchymal transition [ 16 ]. High TRA2A expression is associated with prostate cancer progression [ 17 ]. However, the association between TRA2A and hypoxia in PC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Transformer 2 alpha homolog is a downstream gene of hypoxia-inducible factor 1 subunit alpha and is involved in the progression of pancreatic cancer

et al. 2022

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Intratumoral hypoxia is a common feature of pancreatic cancer (PC) and also plays a role in its progression. However, hypoxia-regulated signatures in PC are still not completely understood. This study aimed to identify core hypoxia-associated genes and determine their underlying molecular mechanisms in PC cells. Transformer 2 alpha homolog (TRA2A) was found to be an important hypoxia-associated gene, which was upregulated in PC tissues and in PC cells cultured under hypoxia. High TRA2A expression was associated with advanced stage, poor differentiation, and lymph node metastasis. Under normoxic and hypoxic conditions, knockdown of TRA2A both markedly suppressed PC cell proliferation and motility in vitro and in vivo , as well as activation of the AKT pathway. Hypoxia-inducible factor 1 subunit alpha (HIF1α) upregulated the transcription of TRA2A by directly binding to its promoter. TRA2A showed a co-expression relationship with HIF1α in PC tissues. Overexpression of TRA2A alleviated the pro-inhibitive functions of HIF1α-inhibition on PC cell proliferation and motility under hypoxia. In conclusion, TRA2A is a crucial downstream gene of HIF1α that accelerates the proliferation and motility of PC cells. TRA2A may be a novel and practical molecular target for investigating the hypoxic response of PC cells. Abbreviations : TRA2A, transformer 2A protein; PC, pancreatic cancer; HIF1α, hypoxia-inducible factor 1-alpha; GEO, Gene Expression Omnibus; IHC, immunohistochemical staining.

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Role of UTX Histone Demethylase in Regulation of MGMT, TRA2A, U2AF1, and RPS6KA2 Genes in Prostate Cancer Cell Lines

Cited by 2 publications

References 5 publications

ncRNAs mediated RPS6KA2 inhibits ovarian cancer proliferation via p38/MAPK signaling pathway

ncRNAs mediated RPS6KA2 inhibits ovarian cancer proliferation via p38/MAPK signaling pathway

Transformer 2 alpha homolog is a downstream gene of hypoxia-inducible factor 1 subunit alpha and is involved in the progression of pancreatic cancer

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