PRRG4 promotes breast cancer metastasis through the recruitment of NEDD4 and downregulation of Robo1

Zhang, Lingling; Qin, Yaqian; Wu, Guang; Wang, Jieyi; Cao, Jianhua; Wang, Yaqi; Wu, Du; Yang, Kaiyan; Zhao, Zhenzhen; He, Licai; Lyu, Jianxin; Li, Hongzhi; Gu, Haihua

doi:10.1038/s41388-020-01494-7

Cited by 24 publications

(29 citation statements)

References 49 publications

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“…In this latter regard, it is of note that DNM2, L1CAM, ROBO1 and ARHGEF7 proteins, the splicing of whose microexons is also altered in CRC, have been found to physically interact with PTK2 and to regulate focal adhesion assembly. [34][35][36][37][38][39] In addition, ARHGEF7 promotes metastasis of CRC through regulation of cancer cell motility. 40 The dysregulation of alternative microexon splicing might thus affect a protein-protein interaction network, leading to modulation of the adhesion, migration and metastatic potential of CRC cells.…”

Section: Discussionmentioning

confidence: 99%

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Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer

Mochizuki

Funayama

Shirota

et al. 2021

Intl Journal of Cancer

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The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome-wide profile of microexon splicing in matched colorectal cancer (CRC) and normal tissue specimens. Out of 1492 microexons comprising 3 to 15 nucleotides, 21 (1%) manifested differential splicing between CRC and normal tissue. The 21 genes harboring the differentially spliced microexons were enriched in gene ontology terms related to cell adhesion and migration. RNA interferencemediated knockdown experiments identified two splicing factors, RBFOX2 and PTBP1, as regulators of microexon splicing in CRC cells. RBFOX2 and PTBP1 were found to directly bind to microexon-containing pre-mRNAs and to control their splicing in such cells. Differential microexon splicing was shown to be due, at least in part, to altered expression of RBFOX2 and PTBP1 in CRC tissue compared to matched normal tissue. Finally, we found that changes in the pattern of microexon splicing were associated with CRC metastasis. Our data thus suggest that altered expression of RBFOX2 and PTBP1 might influence CRC metastasis through the regulation of microexon splicing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer

Mochizuki

Funayama

Shirota

et al. 2021

Intl Journal of Cancer

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“…Reducing the expression of GNG2 can activate c-SRC and promote AKT signaling pathway, which were closely related to breast cancer cell proliferation [91] , invasion and metastasis [92] . Our study found that elevated miR-125b-5p expression in serum exosomes of female CHB patients may lead to the low expression of GNG2 in breast cancer tissue, and breast cancer patients with low expression of GNG2 will lead to a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Understand the role of exosomal miRNA in the development of breast cancer in patients with chronic HBV infection

Xie¹,

Chen²,

Lin³

et al. 2021

Preprint

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Background: Female chronic hepatitis B patients has shown a higher incidence of breast cancer with poorer prognosis, compared to the non-infected female patients. A significant difference in miRNAs expression in serum exosomes has been identified between female patients with chronic HBV infection and non-infected female. Whether this difference could contribute to the differential incidence and development of breast cancer in these female patients has not been fully understood.Methods: Information of exosomal expression of miRNAs (expression profiles of GSE33857) were acquired from the Gene Expression Omnibus (GEO) database. Targeted genes of this miRNAs and the differentially expressed genes of breast cancer in GEPIA V2.0 database was used to obtain the differentially expressed genes (DEGs). Four analytic methods were performed, including functional annotation, protein-protein interaction (PPI) network and module construction, the clinical pathologic parameters analysis, alongsides prognosis analysis.Results: In the serum exsomes, expression of miR-1237-3p and miR-363-3p were down-regulated whilst expression of miR-100-5p, miR-125b-5p, miR-1260a, miR-1287-5p, miR-148a-3p, miR-885-5p and miR-99a-5p were up-regulated in female chronic hepatitis B (CHB) patients. 228 up-regulated genes and 641 down-regulated genes were selected as DEGs. The DEGs involved in several biological processes ranging from cellular response to hormone stimulus. According to the main enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was the pathways in cancer. Our analysis revealed that among the hub genes, CXCL11 was up-regulated and CXCL12, GNG2, LPAR1, GPR17, CXCL1, ADCY5, ADCY3, CX3CL1, S1PR1 were down-regulated. These genes expression levels were verified in UALCAN, Oncomine and HPA database. High expression level of CXCL11 and low expression levels of CXCL12, LPAR1, ADCY3 and CX3CL1 were positively correlated with some clinical pathological parameters that predicted worse prognosis. Kaplan-Meier (K-M) plotter analysis revealed that these genes that showed a low expression level were positively correlated with poor prognosis of breast cancer, and the high expression genes were negatively correlated with poor prognosis of breast cancer.Conclusion: This bioinformatics analysis study explored the mechanisms of chronic HBV related occurrence and development of breast cancer by changing the expression of miRNAs of serum exosomes. It provided novel directions and therapeutic strategy for chronic HBV infection associated occurrence and development of breast cancer in female patients.

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“…Abnormal ROBO1 expression was found in ocular neovascular diseases [127]. Moreover, ROBO1 has been recognized as a tumor suppressor for various cancers [128], including breast cancer (BC). The ROBO1-neutralizing antibody, R5, reportedly had significant inhibitory effects on BC growth and metastasis.…”

Section: Antibody Targets Membrane Protein and Sub-cellular Signalingmentioning

confidence: 99%

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

Song

2022

Life

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Antibodies are a type of protein produced by active B cells in response to antigen stimulation. A series of monoclonal antibodies and neutralizing antibodies have been invented and put into clinical use because of their high therapeutic effect and bright developing insight. Patients with cancer, infectious diseases, and autoimmune diseases can all benefit from antibody therapy. However, the targeting aspects and potential mechanisms for treating these diseases differ. In the treatment of patients with infectious diseases such as COVID-19, neutralizing antibodies have been proposed as reliable vaccines against COVID-19, which target the ACE2 protein by preventing virus entry into somatic cells. Monoclonal antibodies can target immune checkpoints (e.g., PD-L1 and CTLA-4), tyrosine kinase and subsequent signaling pathways (e.g., VEGF), and cytokines in cancer patients (e.g. IL-6 and IL-1β). It is debatable whether there is any connection between the use of antibodies in these diseases. It would be fantastic to discover the related points and explain the burden for the limitation of cross-use of these techniques. In this review, we provided a comprehensive overview of the use of antibodies in the treatment of infectious disease and cancer patients. There are also discussions of their mechanisms and history. In addition, we discussed our future outlook on the use of antibodies.

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PRRG4 promotes breast cancer metastasis through the recruitment of NEDD4 and downregulation of Robo1

Cited by 24 publications

References 49 publications

Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer

Alternative microexon splicing by RBFOX2 and PTBP1 is associated with metastasis in colorectal cancer

Understand the role of exosomal miRNA in the development of breast cancer in patients with chronic HBV infection

A Comparative and Comprehensive Review of Antibody Applications in the Treatment of Lung Disease

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