Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy

Serino, Grazia; Sallustio, Fabio; Cox, Sharon Natasha; Pesce, Francesco; Schena, Francesco Paolo

doi:10.1681/asn.2011060567

Cited by 191 publications

(186 citation statements)

References 47 publications

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“…In our population of patients with IgAN, eventfree survival of composite outcomes was comparable between patients with rare variants in CFHR5 (n=43) and those without rare variants (n=457; P value for log-rank test was P=0.92). increasing microRNA-associated single-nucleotide polymorphisms were found on microRNA target sites within the 39 UTRs of mRNAs, such as hsa-miR-1207-5p in CFHR5 nephropathy, 40 miR-148b in IgAN, 41 and so on. The c.1710*168G.T variant in CFHR5 was at the target site for hsa-miR-2117/hasmiR-4273 binding.…”

Section: Discussionmentioning

confidence: 99%

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

Zhai

Meng

Zhu

et al. 2016

JASN

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A recent genome-wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H-related (CFHRs) genes, as an IgAN susceptibility locus. Abnormal complement activation caused by a mutation in CFHR5 was shown to cause CFHR5 nephropathy, which shares many characteristics with IgAN. To explore the genetic effect of variants in CFHR5 on IgAN susceptibility, we recruited 500 patients with IgAN and 576 healthy controls for genetic analysis. We sequenced all exons and their intronic flanking regions as well as the untranslated regions of CFHR5 and compared the frequencies of identified variants using the sequence kernel association test. We identified 32 variants in CFHR5, including 28 rare and four common variants.

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Section: Discussionmentioning

confidence: 99%

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

Zhai

Meng

Zhu

et al. 2016

JASN

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“…To validate these data, we conducted real-time quantitative PCR using both primary human B cells and cells from the human lymphoma B-cell line that produces IgA1. 20 The expression of C1GALT1 and ST6GalNAcII was not different between the rhTNFSF13-treated and nontreated groups (Figure 8). …”

Section: B Cell Stimulation With Tnfsf13mentioning

confidence: 90%

The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy

Han¹,

Yang

Choi

et al. 2016

JASN

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TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients (n=21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.

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“…miR-378 targeted UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 7 and enhanced the glycosylation of nephronectin, a ligand for integrin α8β1 (30). miR-148 targeted the enzyme core 1 β1, 3-galactosyltransferase 1 and modulated IgA1 O-glycosylation and the level of secreted galactose-deficient IgA1 (31). miR-199a targeted the glycosylation enzyme ST6GAL1, reduced the sialylation of Necl-2, indirectly reduced the protein level of Necl-2, and enhanced ErbB2/ErbB3 signaling (32).…”

Section: Discussionmentioning

confidence: 99%

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

et al. 2016

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Abstract. Breast cancer is a leading cause of cancer-related mortality among women. Altered fucosylation was found to be closely associated with tumorigenesis and metastasis of breast cancer. MicroRNAs (miRNAs) are important regulators of cell proliferation and metastasis, and aberrant miRNA expression has been observed in breast cancer. The present study aimed to evaluate the level of fucosyltransferase IV (FUT4) and miR-493-5p in breast cancer and investigate their relationship. In the present study, we demonstrated the differential expressional profiles of FUT4 and miR-493-5p in 29 clinical breast cancer tissues, matched adjacent tissue samples and two breast carcinoma cell lines (MCF-7 and MDA-MB-231). Briefly, altered expression levels of FUT4 modified the invasive activities and tumorigenicity of the MCF-7 and MDA-MB-231 cells. Further study demonstrated that miR-493-5p plays a role as a suppressor in breast cancer cell invasion and tumorigenicity. Moreover, the expression levels of miR-493-5p were inversely proportional to those of FUT4 both at the mRNA and protein levels. Luciferase reporter assays confirmed that miR-493-5p bound to the 3'-untranslated (3'-UTR) region of FUT4, and inhibited the expression of FUT4 in breast cancer cells. Taken together, our data suggest that FUT4 may have a potential role in the treatment of breast cancer, as well as miR-493-5p is a novel regulator of invasiveness and tumorigenicity of breast cancer cells through targeting FUT4. The miR-493-5p/FUT4 pathway has therapeutic potential in breast cancer. IntroductionBreast cancer is the most common invasive cancer and the second cause of cancer-related death in women (1,2). Each year more than a half a million new cases of breast cancer are diagnosed in the US and Europe (3), and in China. Breast cancer is a very heterogeneous disease. Some patients are cured by the surgical removal of the primary tumor while other patients suffer from metastasis and progression of the disease, despite adjuvant therapy. Therefore, it is essential to develop effective and safer therapeutic modalities against breast cancer.Glycosylation is one of the important steps of protein post-translational modifications, and ~50% of proteins are glycosylated (4). Protein glycosylation plays a role in a variety of cellular biological functions, such as cell-cell and cell-substrate adhesion, membrane organization, cell immunogenicity and protein targeting (5). Specific changes in the glycosylation patterns of cell surface glycoprotein have been shown to enhance the metastatic potential of tumor cells. Aberrant expression of fucosylated glycans has also been detected in various types of tumors.The fucosyltransferase (FUT) family is a group of fucosylation synthases that catalyze the transfer of L-fucose (Fuc) from an activated GDP-β-L-Fuc to various acceptor molecules such as N-acetyllactosamine. The transfer of Fuc residue from the donor substrate, GDP-Fuc, is catalyzed to the oligosaccharide acceptor in a1, a1, FUT4, FUT5, FUT6, FUT7, FUT9, FUT10 and FUT1...

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Abnormal miR-148b Expression Promotes Aberrant Glycosylation of IgA1 in IgA Nephropathy

Abstract: Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA nephropathy. The mechanisms underlying this abnormal glycosylation are not well understood, but reduced expression of the enzyme core 1, b1,3-galactosyltransferase

Cited by 191 publications

References 47 publications

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

Rare Variants in the Complement Factor H–Related Protein 5 Gene Contribute to Genetic Susceptibility to IgA Nephropathy

The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy

miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4

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