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CLC number: R394-3

On-line Access: 2015-03-05

Received: 2014-10-14

Revision Accepted: 2015-01-13

Crosschecked: 2015-02-10

Cited: 2

Clicked: 4422

Citations:  Bibtex RefMan EndNote GB/T7714


Wen-biao Chen


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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.3 P.235-250


Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples

Author(s):  Wen-biao Chen, Jian-rong Huang, Xiang-qi Yu, Xiao-cong Lin, Yong Dai

Affiliation(s):  Clinical Medical Research Center, Shenzhen Peoples Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518020, China; more

Corresponding email(s):   daiyong22@aliyun.com

Key Words:  Alport syndrome, miRNA, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Induced pluripotent stem cells (iPSCs), Solexa sequencing

Wen-biao Chen, Jian-rong Huang, Xiang-qi Yu, Xiao-cong Lin, Yong Dai. Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples[J]. Journal of Zhejiang University Science B, 2015, 16(3): 235-250.

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author="Wen-biao Chen, Jian-rong Huang, Xiang-qi Yu, Xiao-cong Lin, Yong Dai",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples
%A Wen-biao Chen
%A Jian-rong Huang
%A Xiang-qi Yu
%A Xiao-cong Lin
%A Yong Dai
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 3
%P 235-250
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400272

T1 - Identification of microRNAs and their target genes in Alport syndrome using deep sequencing of iPSCs samples
A1 - Wen-biao Chen
A1 - Jian-rong Huang
A1 - Xiang-qi Yu
A1 - Xiao-cong Lin
A1 - Yong Dai
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 3
SP - 235
EP - 250
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400272

MicroRNAs (miRNAs) are a class of small RNA molecules that are implicated in post-transcriptional regulation of gene expression during development. The discovery and understanding of miRNAs has revolutionized the traditional view of gene expression. alport syndrome (AS) is an inherited disorder of type IV collagen, which most commonly leads to glomerulonephritis and kidney failure. Patients with AS inevitably reach end-stage renal disease and require renal replacement therapy, starting in young adulthood. In this study, solexa sequencing was used to identify and quantitatively profile small RNAs from an AS family. We identified 30 known miRNAs that showed a significant change in expression between two individuals. Nineteen miRNAs were up-regulated and eleven were down-regulated. Forty-nine novel miRNAs showed significantly different levels of expression between two individuals. Gene target predictions for the miRNAs revealed that high ranking target genes were implicated in cell, cell part and cellular process categories. The purine metabolism pathway and mitogen-activated protein kinase (MAPK) signaling pathway were enriched by the largest number of target genes. These results strengthen the notion that miRNAs and their target genes are involved in AS and the data advance our understanding of miRNA function in the pathogenesis of AS.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Abrahamson, D.R., Prettyman, A.C., Robert, B., et al., 2003. Laminin-1 reexpression in Alport mouse glomerular basement membranes. Kidney Int., 63(3):826-834.

[2]Abrahamson, D.R., Hudson, B.G., Stroganova, L., et al., 2009. Cellular origins of type IV collagen networks in developing glomeruli. J. Am. Soc. Nephrol., 20(7):1471-1479.

[3]Anders, S., Huber, W., 2010. Differential expression analysis for sequence count data. Genome Biol., 11(10):R106.

[4]Ansorge, W.J., 2009. Next-generation DNA sequencing techniques. N. Biotechnol., 25(4):195-203.

[5]Chen, Y., Luo, R., Xu, Y., et al., 2013. Generation of systemic lupus erythematosus-specific induced pluripotent stem cells from urine. Rheumatol. Int., 33(8):2127-2134.

[6]Chen, Y.H., Wang, S.Q., Wu, X.L., et al., 2013. Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing. Urol. Oncol., 31(2):219-227.

[7]Chung, A.C., Yu, X., Lan, H.Y., 2013. MicroRNA and nephropathy: emerging concepts. Int. J. Nephrol. Renovasc. Dis., 6:169-179.

[8]Colville, D.J., Savige, J., 1997. Alport syndrome. A review of the ocular manifestations. Ophthalmic. Genet., 18(4):161-173.

[9]Dai, Y., Sui, W., Lan, H., et al., 2009. Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol. Int., 29(7):749-754.

[10]de Luca, A., Maiello, M.R., D'Alessio, A., et al., 2012. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin. Ther. Targets, 16(S2):S17-S27.

[11]Gehrs, K.M., Pollock, S.C., Zilkha, G., 1995. Clinical features and pathogenesis of Alport retinopathy. Retina, 15(4):305-311.

[12]Gross, O., Beirowski, B., Koepke, M.L., et al., 2003. Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int., 63(2):438-446.

[13]Gross, O., Licht, C., Anders, H.J., et al., 2012. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int., 81(5):494-501.

[14]Gubler, M.C., Heidet, L., Antignac, C., 2007. Alport syndrome or progressive hereditary nephritis with hearing loss. Nephrol. Ther., 3(3):113-120 (in French).

[15]Hafner, M., Landgraf, P., Ludwig, J., et al., 2008. Identification of microRNAs and other small regulatory RNAs using cDNA library sequencing. Methods, 44(1):3-12.

[16]He, J., Xu, Y., Koya, D., et al., 2013. Role of the endothelial-to-mesenchymal transition in renal fibrosis of chronic kidney disease. Clin. Exp. Nephrol., 17(4):488-497.

[17]Hertz, J.M., 2009. Alport syndrome. Molecular genetic aspects. Dan. Med. Bull., 56(3):105-152.

[18]Jia, W., Chen, W., Kang, J., 2013. The functions of microRNAs and long non-coding RNAs in embryonic and induced pluripotent stem cells. Genomics Proteomics Bioinformatics, 11(5):275-283.

[19]Jo, D.H., Kim, J.H., Park, W.Y., et al., 2011. Differential profiles of microRNAs in retinoblastoma cell lines of different proliferation and adherence patterns. J. Pediatr. Hematol. Oncol., 33(7):529-533.

[20]Kang, D.H., Nakagawa, T., 2005. Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease. Semin. Nephrol., 25(1):43-49.

[21]Kashtan, C.E., 1993. Alport syndrome and thin basement membrane nephropathy. In: Pagon, R.A., Adam, M.P., Ardinger, H.H. (Eds.), GeneReviews. University of Washington, Seattle, WA.

[22]Kashtan, C.E., 1999. Alport syndrome: an inherited disorder of renal, ocular, and cochlear basement membranes. Medicine, 78(5):338-360.

[23]Li, R., Yu, C., Li, Y., et al., 2009. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics, 25(15):1966-1967.

[24]Miner, J.H., 2011. Glomerular basement membrane composition and the filtration barrier. Pediatr. Nephrol., 26(9):1413-1417.

[25]Morozova, O., Marra, M.A., 2008. Applications of next-generation sequencing technologies in functional genomics. Genomics, 92(5):255-264.

[26]Murea, M., 2012. Advanced kidney failure and hyperuricemia. Adv. Chronic Kidney Dis., 19(6):419-424.

[27]O'Connell, S., Tuite, N., Slattery, C., et al., 2012. Cyclosporine A-induced oxidative stress in human renal mesangial cells: a role for ERK1/2 MAPK signaling. Toxicol. Sci., 126(1):101-113.

[28]Pengal, R., Guess, A.J., Agrawal, S., et al., 2011. Inhibition of the protein kinase MK-2 protects podocytes from nephrotic syndrome-related injury. Am. J. Physiol. Renal Physiol., 301(3):F509-F519.

[29]Pfaff, N., Moritz, T., Thum, T., et al., 2012. miRNAs involved in the generation, maintenance, and differentiation of pluripotent cells. J. Mol. Med., 90(7):747-752.

[30]Pohl, M., Danz, K., Gross, O., et al., 2013. Diagnosis of Alport syndrome-search for proteomic biomarkers in body fluids. Pediatr. Nephrol., 28(11):2117-2123.

[31]Punga, T., Le Panse, R., Andersson, M., et al., 2014. Circulating miRNAs in myasthenia gravis: miR-150-5p as a new potential biomarker. Ann. Clin. Transl. Neurol., 1(1):49-58.

[32]Putta, S., Lanting, L., Sun, G., et al., 2012. Inhibiting microRNA-192 ameliorates renal fibrosis in diabetic nephropathy. J. Am. Soc. Nephrol., 23(3):458-469.

[33]Qin, W., Chung, A.C., Huang, X.R., et al., 2011. TGF-β/ Smad3 signaling promotes renal fibrosis by inhibiting miR-29. J. Am. Soc. Nephrol., 22(8):1462-1474.

[34]Steenhard, B.M., Vanacore, R., Friedman, D., et al., 2012. Upregulated expression of integrin α1 in mesangial cells and integrin α3 and vimentin in podocytes of Col4a3-null (Alport) mice. PLoS ONE, 7(12):e50745.

[35]Tan, Y., Ge, G., Pan, T., et al., 2014. A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus. PLoS ONE, 9(9):e107986.

[36]Temme, J., Kramer, A., Jager, K.J., et al., 2012. Outcomes of male patients with Alport syndrome undergoing renal replacement therapy. Clin. J. Am. Soc. Nephrol., 7(12):1969-1976.

[37]Thorner, P.S., 2007. Alport syndrome and thin basement membrane nephropathy. Nephron Clin. Pract., 106(2):c82-c88.

[38]Trionfini, P., Benigni, A., Remuzzi, G., 2015. MicroRNAs in kidney physiology and disease. Nat. Rev. Nephrol., 11(1):23-33.

[39]Tryggvason, K., Zhou, J., Hostikka, S.L., et al., 1993. Molecular genetics of Alport syndrome. Kidney Int., 43(1):38-44.

[40]Zhang, K.W., Colville, D., Tan, R., et al., 2008. The use of ocular abnormalities to diagnose X-linked Alport syndrome in children. Pediatr. Nephrol., 23(8):1245-1250.

[41]Zhang, X., Yan, Z., Zhang, J., et al., 2011. Combination of hsa-miR-375 and hsa-miR-142-5p as a predictor for recurrence risk in gastric cancer patients following surgical resection. Ann. Oncol., 22(10):2257-2266.

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