RSK1 promotes murine breast cancer growth and metastasis

Czaplińska, Dominika; Gorska, Monika; Mieczkowski, Kamil; Peszyńska-Sularz, Grażyna; Żaczek, Anna; Romańska, Hanna; Sądej, Rafał

doi:10.5603/fhc.a2018.0001

Cited by 6 publications

(6 citation statements)

References 30 publications

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“…ESR1 is a telomerase activating factor that binds to the hTERT promoter and its role in EC is well established [ 47 , 217 , 225 ]. The identification of RPS6KA1 and WFS1 is interesting as previous studies have reported their role in the promotion of tumour progression and metastasis in various cancers [ 226 , 227 , 228 , 229 ]. The role of ANAPC4 in cancer has not been studied in detail.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

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Hill

et al. 2020

MPs

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Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including NOP56, WFS1, ANAPC4 and TUBB4A. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.

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Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

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Hill

et al. 2020

MPs

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“…c‐Jun, PRAS40, RSK‐1, and RSK‐2 are common phosphokinases in cancer progression 35–37 . However, by western blot analysis, we found the total protein levels of c‐jun also changed and the proportion of p‐c‐jun/c‐jun, p‐PRAS40/PRAS40, p‐RSK‐1/RSK, and p‐RSK‐2/RSK does not change significantly.…”

Section: Discussionmentioning

confidence: 67%

“…c-Jun, PRAS40, RSK-1, and RSK-2 are common phosphokinases in cancer progression. [35][36][37] However, by western blot analysis, we found the total protein levels of c-jun also changed and the proportion of p-c-jun/c-jun, p-PRAS40/PRAS40, p-RSK-1/RSK, and p-RSK-2/RSK does not change significantly. c-Myc is an established proto-oncogene that can promote cell survival and proliferation, and cyclin D1 is an important cell cycle regulator.…”

Section: Discussionmentioning

confidence: 99%

The HDAC2–MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c‐Myc and cyclin D1

Wang

Shen

Pan

et al. 2023

Molecular Carcinogenesis

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Genome‐wide association studies have identified numerous single‐nucleotide polymorphisms (SNPs) associated with lung cancer; however, the functions of histone deacetylase 2 (HDAC2) rs13213007 and HDAC2 in nonsmall cell lung cancer (NSCLC) remain unclear. Here we identified HDAC2 rs13213007 as a risk SNP and showed that HDAC2 was upregulated in both peripheral blood mononuclear cells (PBMCs) and NSCLC tissues with the rs13213007 A/A genotype compared with those with the rs13213007 G/G or G/A genotype. Patient clinical data indicated strong associations between rs13213007 genotype and N classification. Immunohistochemical staining confirmed that higher expression of HDAC2 was associated with NSCLC progression. Furthermore, we generated 293T cells with the rs13213007 A/A genotype using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 gene editing. Chromatin immunoprecipitation sequencing followed by motif analysis showed that HDAC2 can bind to c‐Myc in rs13213007 A/A 293T cells. Cell Counting Kit‐8, colony formation, wound‐healing, and Transwell assays revealed that HDAC2 upregulates c‐Myc and cyclin D1 expression and promotes NSCLC cell proliferation, migration, and invasion. Co‐immunoprecipitation, quantitative reverse transcription–polymerase chain reaction, and western blot analysis assays showed that MTA3 interacts with HDAC2, decreases HDAC2 expression, and rescues the migration and invasion abilities of NSCLC cells. Taken together, these findings identify HDAC2 as a potential therapeutic biomarker in NSCLC.

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“…protein S6 kinase (RPS6K) (Li et al, 2012;Czaplinska et al, 2018). The RPS6K family is reported to be involved in a lot of pathways, which are important for tumor occurrence and progression (Hajj et al, 2020;Lai et al, 2020;Yang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of miR-138-5p/RPS6KA1-AP2M1 Is Associated With Poor Prognosis in AML

Chen

et al. 2021

Front. Cell Dev. Biol.

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Acute myeloid leukemia (AML) is a malignant disease of hematopoietic stem/progenitor cells, and most AML patients are in a severe state. Internal tandem duplication mutations in FLT3 gene (FLT3-ITD) detected in AML stem cells account for 20–30 percent of AML patients. In this study, we attempted to study the impact of the interaction of FLT3-ITD mutation and the CXCL12/CXCR4 axis in AML, and the possible mechanisms caused by the impact by bioinformatics. Gene set variation analysis (GSVA) revealed that the PI3K-Akt-mTOR pathway positively correlated with the status of FLT3-ITD mutation. Multiple survival analyses were performed on TCGA-AML to screen the prognostic-related genes, and RPS6KA1 and AP2M1 are powerful prognostic candidates for overall survival in AML. WGCNA, KEGG/GO analysis, and the functional roles of RPS6KA1 and AP2M1 in AML were clarified by correlation analysis. We found that the expression levels of RPS6KA1 and AP2M1 were significantly associated with chemoresistance of AML, and the CXCL12/CXCR4 axis would regulate RPS6KA1/AP2M1 expression. Besides, miR-138-5p, regulated by the CXCL12/CXCR4 axis, was the common miRNA target of RPS6KA1 and AP2M1. Taken together, the interaction of FLT3-ITD mutation and the CXCL12/CXCR4 axis activated the PI3K-Akt-mTOR pathway, and the increased expression of RPS6KA1 and AP2M1 caused by hsa-miR-138-5p downregulation regulates the multi-resistance gene expression leading to drug indications.

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RSK1 promotes murine breast cancer growth and metastasis

Cited by 6 publications

References 30 publications

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

The HDAC2–MTA3 interaction induces nonsmall cell lung cancer cell migration and invasion by targeting c‐Myc and cyclin D1

Dysregulation of miR-138-5p/RPS6KA1-AP2M1 Is Associated With Poor Prognosis in AML

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