scholarly journals Nuclear Receptor Interacting Protein-2 Mediates the Stabilization and Activation of β-Catenin During Podocyte Injury

2021 ◽  
Vol 9 ◽  
Author(s):  
Qing Hou ◽  
Weibo Le ◽  
Shuyan Kan ◽  
Jinsong Shi ◽  
Yue Lang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Nuclear Receptor ◽  
Protein Interactions ◽  
Wnt Pathway ◽  
Expression Data ◽  
Podocyte Injury ◽  
Interacting Protein ◽  
Chemical Treatments ◽  
Geo Dataset

Objective: Activation of β-catenin causes podocyte injury and proteinuria, but how β-catenin signalling is regulated during podocyte injury remains elusive. Nuclear receptor interacting protein 2 (NRIP2) modulates the Wnt pathway in colorectal cancer-initiating cells, but the role of NRIP2 in podocyte injury has not yet been investigated. We aimed to examine the interaction between NRIP2 and β-catenin signalling.Materials and Methods: Knockdown or overexpression of NRIP2 and β-catenin and chemical treatments were performed in cultured human podocytes. Immunoprecipitation, immunoblotting and immunofluorescence assays were used to assess protein interactions and expression. Data from the GEO dataset and kidney tissues from patients with focal segmental glomerulosclerosis (FSGS) and surgical nephrectomy were examined. An adriamycin (ADR) nephropathy model was established in NRIP2 knockout mice.Results: NRIP2 knockdown accelerated β-catenin degradation, which was reversed by MG132; specifically, NRIP2 bound β-catenin and stabilized it to prevent its degradation through the ubiquitin proteasomal pathway. Overexpression of NRIP2 led to β-catenin activation and Snail1 induction, and these effects were attenuated by β-catenin knockdown. NRIP2 knockdown blocked ADR-stimulated β-catenin activation. In ADR mice, genetic knockout of Nrip2 ameliorated podocyte injury and loss, glomerulosclerosis, and proteinuria by inhibiting β-catenin activation. Moreover, NRIP2 was significantly upregulated in podocytes of FSGS patients and colocalized with nuclear β-catenin.Conclusion: These results established NRIP2 as a stabilizer of β-catenin activation through the ubiquitin proteasomal pathway in podocyte injury.

scholarly journals RACK1 Acts as a Potential Tumor Promoter in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Xue-Yang Li ◽  
Yi Hu ◽  
Nian-Shuang Li ◽  
Jian-Hua Wan ◽  
Yin Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
The Cancer Genome Atlas ◽  
Biological Role ◽  
Tumor Promoter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Normal Tissues ◽  
Geo Dataset

Background. The receptor of activated protein kinase C 1 (RACK1) promotes the progression and invasion of several cancers. However, the role of RACK1 in the pathogenesis of colorectal cancer (CRC) has not been clearly defined. Herein, we aimed to investigate the biological role of RACK1 in CRC. Materials and Methods. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset were searched, and the expression of RACK1 in CRC tissues and adjacent normal tissues was evaluated. Immunohistochemical staining was performed to detect the expression of RACK1 in human CRC, adenoma, and normal tissues. Western blotting was used to detect the expression of RACK1 in human CRC cell lines. Functional assays, such as BrdU, colony formation, and wound healing and transwell invasion assays, were used to explore the biological role of RACK1 in CRC. Results. RACK1 was upregulated in CRC tissues compared with its expression in adjacent normal tissues in TCGA and the GEO dataset (P<0.05). Moreover, RACK1 was significantly overexpressed in CRC and adenoma tissues compared with its expression in normal tissues (P<0.05). Loss-of-function experiments showed that RACK1 promoted cell proliferation, migration, and invasion in vitro. Conclusions. Our data indicated that RACK1, as an oncogene, markedly promoted the progression of CRC, which suggested that RACK1 is a potential therapeutic target for CRC management.

scholarly journals DDX10 Promotes the Proliferation and Metastasis of Colorectal Cancer Cells via Splicing RPL35

2021 ◽  
Author(s):  
Xin Zhou ◽  
Zhihong Liu ◽  
Cuifeng Zhang ◽  
Manman Jiang ◽  
Yuxiao Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Migration And Invasion ◽  
Ppi Network ◽  
Interacting Protein ◽  
Network Analyses ◽  
Potential Biomarker

Abstract Background: Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated.Methods: In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC-MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR.Results: In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC-MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC.Conclusions: In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.

Dietary Choices Modulate Colorectal Cancer Stem Cells: A Role of FXR Nuclear Receptor

2020 ◽  
pp. 1-8
Author(s):  
Nilesh Kumar Sharma ◽  
Sachin C. Sarode ◽  
Gargi S Sarode ◽  
Shankargouda Patil ◽  
Jayanta K. Pal
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Nuclear Receptor ◽  
Dietary Choices ◽  
Colorectal Cancer Stem Cells

scholarly journals Expression and role of nuclear receptor coregulators in colorectal cancer

2017 ◽  
Vol 23 (25) ◽  
pp. 4480 ◽  
Author(s):  
Mouna Triki ◽  
Marion Lapierre ◽  
Vincent Cavailles ◽  
Raja Mokdad-Gargouri
Keyword(s):  
Colorectal Cancer ◽  
Nuclear Receptor ◽  
Nuclear Receptor Coregulators

scholarly journals MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction

2017 ◽  
Vol 312 (4) ◽  
pp. F589-F598 ◽  
Author(s):  
Yan Guo ◽  
Xu Deng ◽  
Shuang Chen ◽  
Lingyun Yang ◽  
Jiajia Ni ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Early Event ◽  
Dependent Manner ◽  
Podocyte Injury ◽  
Interacting Protein ◽  
Adenovirus E1b ◽  
Induced Apoptosis

MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podocytes. In agreement with this finding, miR-30e silencing led to significant podocyte apoptosis. Mitochondrial dysfunction (MtD) has been shown to be an early event in Aldo-induced podocyte injury. Here we found that overexpression of miR-30e improved Aldo-induced MtD while miR-30e silencing resulted in MtD. Next, we found that miR-30e could directly target the BCL2/adenovirus E1B-interacting protein 3-like (BNIP3L) gene. Aldo markedly enhanced BNIP3L expression in podocytes, and silencing of BNIP3L largely abolished Aldo-induced MtD and cell apoptosis. On the contrary, overexpression of BNIP3L induced MtD and apoptosis in podocytes. Together, these findings demonstrate that miR-30e protects mitochondria and podocytes from Aldo challenge by targeting BNIP3L.

scholarly journals A244 ROLE OF THE NUCLEAR RECEPTOR HNF4α AND ITS MANY ISOFORMS IN COLORECTAL CANCER

2018 ◽  
Vol 1 (suppl_2) ◽  
pp. 356-357
Author(s):  
E Lambert ◽  
J Babeu ◽  
D Levesque ◽  
F Boisvert ◽  
F Boudreau
Keyword(s):  
Colorectal Cancer ◽  
Nuclear Receptor

scholarly journals Sip1, a Novel RS Domain-Containing Protein Essential for Pre-mRNA Splicing

1998 ◽  
Vol 18 (2) ◽  
pp. 676-684 ◽  
Author(s):  
Wan-Jiang Zhang ◽  
Jane Y. Wu
Keyword(s):  
Protein Interactions ◽  
Rna Binding ◽  
Sequence Similarity ◽  
Functional Characterization ◽  
Nuclear Extract ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
Splicing Factors ◽  
Interacting Protein

ABSTRACT Previous studies have shown that protein-protein interactions among splicing factors may play an important role in pre-mRNA splicing. We report here identification and functional characterization of a new splicing factor, Sip1 (SC35-interacting protein 1). Sip1 was initially identified by virtue of its interaction with SC35, a splicing factor of the SR family. Sip1 interacts with not only several SR proteins but also with U1-70K and U2AF65, proteins associated with 5′ and 3′ splice sites, respectively. The predicted Sip1 sequence contains an arginine-serine-rich (RS) domain but does not have any known RNA-binding motifs, indicating that it is not a member of the SR family. Sip1 also contains a region with weak sequence similarity to the Drosophila splicing regulator suppressor of white apricot (SWAP). An essential role for Sip1 in pre-mRNA splicing was suggested by the observation that anti-Sip1 antibodies depleted splicing activity from HeLa nuclear extract. Purified recombinant Sip1 protein, but not other RS domain-containing proteins such as SC35, ASF/SF2, and U2AF65, restored the splicing activity of the Sip1-immunodepleted extract. Addition of U2AF65 protein further enhanced the splicing reconstitution by the Sip1 protein. Deficiency in the formation of both A and B splicing complexes in the Sip1-depleted nuclear extract indicates an important role of Sip1 in spliceosome assembly. Together, these results demonstrate that Sip1 is a novel RS domain-containing protein required for pre-mRNA splicing and that the functional role of Sip1 in splicing is distinct from those of known RS domain-containing splicing factors.

scholarly journals The role of the class I Wnt pathway antagonist sFRP4 in colorectal cancer

2019 ◽  
Vol 2 ◽  
pp. 18-18
Author(s):  
Yuting Liu ◽  
Jianfeng Li ◽  
Jian Qi
Keyword(s):  
Colorectal Cancer ◽  
Wnt Pathway ◽  
Class I

scholarly journals TMEM100 Modulates TGF-β Signaling Pathway to Inhibit Colorectal Cancer Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Huixia Li ◽  
Chuan Cheng ◽  
Weibo You ◽  
Jiujian Zheng ◽  
Jie Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Transmembrane Protein ◽  
Expression Data ◽  
Mrna Expression Data ◽  
Colorectal Cancer Progression ◽  
Inhibitor Gene

Objectives. This study investigated the functional mechanism of transmembrane protein 100 (TMEM100) as a tumor inhibitor gene in CRC cells and offered a reference for the treatment of CRC. Methods. The mRNA expression data of CRC were acquired from the TCGA database to mine differentially expressed mRNAs. The role of TMEM100 in the progression of CRC cells was evaluated by MTT, colony formation, scratch healing, and Transwell assays. The influence of TMEM100 on the TGF-β signaling pathway was detected by western blot. Results. TMEM100 was markedly lowly expressed in CRC. CRC cell growth was significantly suppressed by overexpressing TMEM100 but noticeably facilitated by silencing TMEM100. Overexpression of TMEM100 inhibited the activation of the TGF-β signaling pathway, thus inhibiting malignant progression of CRC. Conclusion. TMEM100 is lowly expressed in CRC, which can suppress CRC cell growth by regulating the TGF-β signaling pathway.

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