Smad4 suppresses the progression of renal cell carcinoma via the activation of forkhead box protein H1

Liu, Yunli; Xu, Yangyang; Li, Xuedong; Chen, Zhaoyan

doi:10.3892/mmr.2014.3061

Cited by 9 publications

(4 citation statements)

References 27 publications

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“…However, data from TCGA database showed that SMAD4 was downregulated in RCC tissues compared with normal tissues and patients with lower SMAD4 levels had worse overall survival time. As we all know, SMAD4 had been recognized as a tumor suppressor gene in a good deal of cancers, and recent study had presented that SMAD4 suppressed the progression of RCC by targeting various downstream genes [ 40 – 42 ]. The reason for such inconsistency remained an enigma.…”

Section: Discussionmentioning

confidence: 99%

Sunitinib-suppressed miR-452-5p facilitates renal cancer cell invasion and metastasis through modulating SMAD4/SMAD7 signals

Zhai

Zhang

et al. 2018

Mol Cancer

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PurposeAlthough microRNAs (miRNAs) were revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment was limited. Here we sought to identify human miRNAs that acted as key regulators in renal cancer metastasis and Sunitinib treatment.Experimental designWe focused on 2 published microarray data to select out our anchored miRNA and then explored the roles of miR-452-5p both in vitro and in vivo, which was downregulated after Sunitinib treatment while upregulated in metastasis renal cell carcinoma (RCC) tissues.ResultsHere, we discovered that treating with Sunitinib, the targeted receptor tyrosine kinase inhibitor (TKI), inhibited renal cancer cell migration and invasion via attenuating the expression of miR-452-5p. The novel identified miR-452-5p was upregulated and associated with poor prognosis in RCC. Preclinical studies using multiple RCC cells and xenografts model illustrated that miR-452-5p could promote RCC cell migration and invasion in vitro and in vivo. Mechanistically, P65 could directly bind to the miR-452-5p promoter and thus transcriptionally induce miR-452-5p expression, which led to post-transcriptionally abrogate SMAD4 expression, thus inhibition of its downstream gene SMAD7.ConclusionOur study presented a road map for targeting this newly identified miR-452-5p and its SMAD4/SMAD7 signals pathway, which imparted a new potential therapeutic strategy for mRCC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0906-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Sunitinib-suppressed miR-452-5p facilitates renal cancer cell invasion and metastasis through modulating SMAD4/SMAD7 signals

Zhai

Zhang

et al. 2018

Mol Cancer

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“…Previous study has demonstrated that TGF-β can act as an important factor in the progression of renal fibrosis. 31 Liu et al 32 further identified FOXH1 as a transcription regulator for Smads, which are the core element of the intracellular signaling pathway of TGF-β ligands, indicating that FOXH1 might have a key role in the development of renal fibrosis. Thus, cis- and trans-regulation predictions of our research may imply novel perspectives into the molecular mechanisms of CKD.…”

Section: Discussionmentioning

confidence: 99%

Identification of circulating lncRNA in chronic kidney disease based on bioinformatics analysis

Huang

Sun

2022

Exp Biol Med (Maywood)

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Chronic kidney disease (CKD) is a high mortality disease and generally remains asymptomatic in the early stages. Long non-coding RNA (lncRNA) is defined as a non-protein-coding transcript more than 200 nucleotides which participate in numerous biological processes and have been identified as novel diagnostic markers for many diseases. Detection of circulating lncRNAs is a rapidly evolving, new area of molecular diagnosis. The purpose of our research was to identify circulating lncRNA expression profiles and possible molecular mechanisms involved in CKD. Blood samples were obtained from patients with CKD and healthy volunteers, and high-throughput sequencing was performed to identify differentially expressed (DE) lncRNAs and mRNAs. DE lncRNAs and mRNAs in peripheral blood mononuclear cells (PBMCs) were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to ensure the reliability and validity of RNA-seq data. Bioinformatics analysis was used to obtain biological functions and key pathways related to the pathogenesis of CKD. The interaction and co-expression functional networks for DE lncRNAs and mRNAs were also constructed. Our data showed that of the 425 DE lncRNAs detected, 196 lncRNAs were upregulated, while that of 229 lncRNAs were downregulated. A total of 433 DE mRNAs were identified in patients with CKD compared to healthy individuals. GO analysis revealed that DE lncRNAs were highly correlated with binding and pathway regulation. KEGG analysis suggested that DE lncRNAs were obviously enriched in regulatory pathways, such as antigen processing and presentation. We successfully constructed a potential DE lncRNA-mRNA co-expression network and analyzed the target genes of DE lncRNAs to predict cis- and trans-regulation in CKD. 100 lncRNAs that corresponded to 14 transcription factors (TFs) were identified in the TF-lncRNA binary network. Our findings on the lncRNA expression profiles and functional networks may help to interpret the possible molecular mechanisms implied in the pathogenesis of CKD; the results demonstrated that lncRNAs could potentially to be used as diagnostic biomarkers in CKD.

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“…EMT drives metastasis in the progression of multiple cancer types, including lung cancer [ 20 , 21 ]. EMT is stimulated under conditions where epithelial cells lose connexins, such as E-cadherin, and acquire mesenchymal markers, such N-cadherin and vimentin [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

FOXH1 promotes lung cancer progression by activating the Wnt/β-catenin signaling pathway

Zhang

Yang

et al. 2021

Cancer Cell Int

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Background The expression of forkhead box protein H1 (FOXH1) is frequently upregulated in various cancers. However, the molecular mechanisms underlying the association between FOXH1 expression and lung cancer progression still remain poorly understood. Thus, the main objective of this study is to explore the role of FOXH1 in lung cancer. Methods The Cancer Genome Atlas dataset was used to investigate FOXH1 expression in lung cancer tissues, and the Kaplan–Meier plotter dataset was used to determine the role of FOXH1 in patient prognosis. A549 and PC9 cells were transfected with short hairpin RNA targeting FOXH1 mRNA. The Cell Counting Kit-8, colony formation, soft agar, wound healing, transwell invasion and flow cytometry assays were performed to evaluate proliferation, migration and invasion of lung cancer cells. Tumorigenicity was examined in a BALB/c nude mice model. Western blot analysis was performed to assess the molecular mechanisms, and β-catenin activity was measured by a luciferase reporter system assay. Results Higher expression level of FOXH1 was observed in tumor tissue than in normal tissue, and this was associated with poor overall survival. Knockdown of FOXH1 significantly inhibited lung cancer cell proliferation, migration, invasion, and cycle. In addition, the mouse xenograft model showed that knockdown of FOXH1 suppressed tumor growth in vivo. Further experiments revealed that FOXH1 depletion inhibited the epithelial-mesenchymal transition of lung cancer cells by downregulating the expression of mesenchymal markers (Snail, Slug, matrix metalloproteinase-2, N-cadherin, and Vimentin) and upregulating the expression of an epithelial marker (E-cadherin). Moreover, knockdown of FOXH1 significantly downregulated the activity of β-catenin and its downstream targets, p-GSK-3β and cyclin D1. Conclusion FOXH1 exerts oncogenic functions in lung cancer through regulation of the Wnt/β-catenin signaling pathway. FOXH1 might be a potential therapeutic target for patients with certain types of lung cancer.

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Smad4 suppresses the progression of renal cell carcinoma via the activation of forkhead box protein H1

Cited by 9 publications

References 27 publications

Sunitinib-suppressed miR-452-5p facilitates renal cancer cell invasion and metastasis through modulating SMAD4/SMAD7 signals

Sunitinib-suppressed miR-452-5p facilitates renal cancer cell invasion and metastasis through modulating SMAD4/SMAD7 signals

Identification of circulating lncRNA in chronic kidney disease based on bioinformatics analysis

FOXH1 promotes lung cancer progression by activating the Wnt/β-catenin signaling pathway

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