PBX1 promotes the cell proliferation via JAK2/STAT3 signaling in clear cell renal carcinoma

Wei, Xin; Yu, Lili; Li, Yi

doi:10.1016/j.bbrc.2018.04.127

Cited by 30 publications

(27 citation statements)

References 22 publications

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“…For treating RCC, JAK2/STAT3 has been recognized as an important target. A recent study showed that activation of JAK2/STAT3 signaling pathway promotes cell proliferation in CCRCC [82]. According to Xin et al, treatment of 786-O human renal cancer cells with AZD1480 showed only limited decrease in cell viability.…”

Section: Discussionmentioning

confidence: 99%

Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

Kang

Lee

et al. 2019

Cancers

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Specific kinds of interleukin (IL) receptors are known to mediate lymphocyte proliferation and survival. However, recent reports have suggested that the high expression of IL4Rα and IL13Rα1 in tumor tissue might be associated with tumorigenesis in several kinds of tumor. We found that a significant association between mRNA level of IL4Rα or IL13Rα1 and the poor prognosis of renal cell carcinoma (RCC) from the public database (http://www.oncolnc.org/). Then, we evaluated the clinicopathological significance of the immunohistochemical expression of IL4Rα and IL13Rα1 in 199 clear cell RCC (CCRCC) patients. The individual and co-expression patterns of IL4Rα and IL13Rα1 were significantly associated with cancer-specific survival (CSS) and relapse-free survival (RFS) in univariate analysis. Multivariate analysis indicated IL4Rα-positivity and co-expression of IL4Rα and IL13Rα1 as the independent indicators of shorter CSS and RFS of CCRCC patients. For the in vitro evaluation of the oncogenic role of IL4Rα and IL13Rα1 in RCC, we knock-downed IL4Rα or IL13Rα1 and observed that the cell proliferation rate was decreased, and the apoptosis rate was increased in A498 and ACHN cells. Furthermore, we examined the possible role of Janus kinase 2 (JAK2), well-known down-stream tyrosine kinase under the heterodimeric receptor complex of IL4Rα and IL13Rα1. Interestingly, JAK2 interacted with Forkhead box O3 (FOXO3) to cause tyrosine-phosphorylation of FOXO3. Silencing IL4Rα or JAK2 in A498 and ACHN cells reduced the interaction between JAK2 and FOXO3. Moreover, pharmacological inhibition of JAK2 induced the nuclear localization of FOXO3, leading to increase apoptosis and decrease cell proliferation rate in A498 and ACHN cells. Taken together, these results suggest that IL4Rα and IL13Rα1 might be involved in the progression of RCC through JAK2/FOXO3 pathway, and their expression might be used as the novel prognostic factor and therapeutic target for RCC patients.

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Section: Discussionmentioning

confidence: 99%

Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

Kang

Lee

et al. 2019

Cancers

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“…STAT3 is a potential transcription factor that mediates extracellular signals, such as cytokines and growth factors, by interacting with cell surface polypeptide receptors. Studies have shown that STAT3 promotes RCC occurrence and development (62)(63)(64). STAT3 responds to extracellular stimuli and is activated after tyrosine phosphorylation.…”

Section: Important Inflammation-related Pathways In the Development Of Rccmentioning

confidence: 99%

Impact of inflammation and immunotherapy in renal cell carcinoma (Review)

et al. 2020

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Substantial research attention has been directed at exploring the mechanisms and treatment of renal cell carcinoma (RCC). Indeed, the association between inflammation and tumor phenotypes has been at the center of cancer research. Concomitant with research on the inflammation response and inflammatory molecules involved in RCC, new breakthroughs have emerged. A large body of knowledge now shows that treatments targeting inflammation and immunity in RCC provide substantial clinical benefits. Adequate analysis and a better understanding of the mechanisms of inflammatory factors in the occurrence and progression of RCC are highly desirable. Currently, numerous RCC treatments targeted at inflammation and immunotherapy are available. The current review describes in detail the link between inflammation and RCC.

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“…Previous analyses of this gene have linked differential methylation patterns to higher birth weight-for-gestational age (67) and a translocational rearrangement of this gene and TCF3/E2A has been associated with B-cell acute lymphoblastic leukaemia (68). Additionally, PBX1 haploinsufficiency has been linked to congenital anomalies of the kidney and urinary tract (69), reported to be involved in the proliferation of cells in renal cell carcinoma (70) and has been recognised as a candidate gene for T2DM (66,71).…”

Section: Discussionmentioning

confidence: 99%

Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease

Smyth

Kilner

Nair

et al. 2020

Preprint

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A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), which is the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n=862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p≤x10-8 and fold change ±2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Top-ranked genes within which several dmCpGs were located and supported by in silico functional data, and replication where possible, include; AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9, and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Epigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals, has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

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PBX1 promotes the cell proliferation via JAK2/STAT3 signaling in clear cell renal carcinoma

Cited by 30 publications

References 22 publications

Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

Interleukin4Rα (IL4Rα) and IL13Rα1 Are Associated with the Progress of Renal Cell Carcinoma through Janus Kinase 2 (JAK2)/Forkhead Box O3 (FOXO3) Pathways

Impact of inflammation and immunotherapy in renal cell carcinoma (Review)

Assessment of differentially methylated loci in individuals with end-stage kidney disease attributed to diabetic kidney disease

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