Cyclic RNA expression and disease correlation in lupus erythematosus

Yunxu Bio has frequently received customer news reports for several weeks, and the work in various fields has blossomed. After the publication of the 10-minute RNA methylation article , circular RNA research has been published in excellent articles. We have been analyzing cloud-based client circular RNA for two weeks, including the world's first mouse brain traumatic exocytosis. Research on ring-shaped RNA and the world's first research on Xenopus laevis circular RNA . This week, we brought you the latest work of Professor Zhou Hua, the first hospital affiliated to China Medical University. The circular RNA-CircHLA-C plays a role in lupus nephritis (LN) through competitive adsorption of miR-150. To an important role. This article was recently published in the Cell publication "Molecular Therapy Nucleic Acids" ( impact factor 6.392 ) .

Research Background:

Circular RNA is a new class of non-coding RNAs that have been studied in a variety of tissues and diseases, but studies have not been conducted in glomerular and tubulointerstitial diseases. This article focuses on the regulation of circular RNA in the treatment of lupus erythematosus. It is known that circular RNA mainly exerts physiological functions by miRNA sponge mechanism, and regulates the occurrence and development of diseases by competitively binding miRNA. The previous study found that miR-150 plays a regulatory role in lupus erythematosus. This paper relies on high-throughput sequencing combined with biosignal analysis (the circular RNA sequencing work provided by Yunxu Biotechnology) to find CircHLA-C with differential expression in disease. It can specifically bind to miR-150 and synergistically regulate lupus erythematosus.

Research ideas:

Previous work by the authors showed that miR-150 expression was positively correlated with renal failure syndrome in patients with lupus erythematosus (LN). In this work, the authors hope to find a circular RNA molecule that acts in concert with miR-150 to regulate LN. Therefore, the authors selected 7 cases of LN kidney tissue and 6 normal kidney tissues for circular RNA sequencing, and identified 171 significant differentially expressed circular RNA molecules. Ten circular RNA molecules were selected for qPCR verification, and 7 cases were consistent with the sequencing results. Among them, CircHLA-C expression has a positive correlation with clinical indicators of nephropathy, proteinuria, serum creatinine and renal tissue activity. In the disease group, CircHLA-C expression increased by 2.72 times and miR-150 decreased by 66%. The biomarker prediction showed that CircHLA-C has a binding site with miR-150, and the expression of both has a negative correlation. The authors have demonstrated for the first time that in the lupus erythematosus, the circular RNA, CircHLA-C, may competitively bind to miR-150 through the sponge mechanism, affecting the development of the disease.

Study 1: Cyclic RNA expression profile

The ratio of male to female in LN patients was 9:1. Therefore, when the authors collected clinical samples, 6 females and 1 male LN grade IV nephropathy were selected for study. The authors mapped the LN disease circular RNA expression profile by high-throughput sequencing of the disease and normal groups. A total of 18505 expression changes in circular RNA were detected in the spectrum, of which 11411 cases were up-regulated (142 significantly up-regulated, FC>=2, p-Value <=0.05), and 7094 cases were down-regulated (29 significantly down-regulated, FC<=2, p-Value < =0.05). Of the 171 significant differentially expressed circular RNAs, a total of 39 were found for the first time. It is found that these circular RNAs are mostly less than 2000 nt in length and exhibit full coverage of chromosome distribution. Overall, 76.6% of the differential circular RNAs were exon-derived circular RNA, 16.4% were Sense overlapping-derived circular RNA, and 7% were other sources of circular RNA.

Study 2: Prediction of circular RNA function

At present, the main mechanism of action of circular RNA in vivo is miRNA sponge. The authors have confirmed that miRNAs such as miR-150 play important roles in LN disease. Therefore, the authors selected 40 circularly significant differential expressions (20 most up-regulated and 20 most down-regulated), and mapped their interaction with miRNA. The biosignal layer predicted the possible miRNAs of circular RNA. Sponge function. Subsequently, the authors predicted the cellular functions and signaling pathways of these differentially expressed circular RNAs in vivo through GO analysis and KEGG analysis. GO results showed that differentially up-regulated circular RNA-derived target genes are closely related to dendritic cell differentiation and mRNA splicing. The KEGG results showed that the differentially regulated circular RNA-derived target genes are mainly involved in the HIF-1 signaling pathway and the NF-κB signaling pathway, which are important regulators in LN.

Study 3: Circular RNA Validation

High-throughput data requires low-throughput techniques to complement validation. The authors selected 10 differentially expressed circular RNAs for qPCR verification, 7 of which were consistent with sequencing results. In order to identify the ring RNA associated with kidney disease, the authors verified the consistency of these 7 cases of circular RNA and clinical indicators of nephropathy. CircHLA-C and proteinuria (r=0.920, p=0.009), serum creatinine (r=0.756, p=0.082) crescent glomerular % (r=0.929, p=0.007) and renal activity index were found. (r = 0.884, p = 0.020) is positively correlated.

Study 4: Interaction of circular RNA with miRNA

In this part of the work, the authors studied the results of previous miRNA research and circular RNA. Renal biopsy results showed that miR-150 expression was significantly down-regulated in LN tissues, and miR-150 expression was negatively correlated with circHLA-C. The authors used TargetScan and miRanda analysis to find a highly reliable binding site between circHLA-C and miR-150.

Conclusion:

Based on high-throughput sequencing technology, this paper first identified the specific circular RNA expression profile of lupus erythematosus. The CircHLA-C identified in this paper is a new circular RNA closely related to kidney disease. It will be of great significance to carry out molecular marker analysis and molecular mechanism research.

Original: CircHLA-C Plays an Important Role in Lupus Nephritis by Sponging miR-150, DOI: 10.1016/j.omtn.2017.12.006

About the Author:

Zhou Hua, Chief Physician, Professor, Doctoral Supervisor, the fifth batch of climbing scholars in Liaoning Province, and the second batch of winners of the “Ten Thousand High-end Talents Introduction Project” in Liaoning Province. He received his Ph.D. degree in nephrology from Japan. He has been engaged in scientific research and clinical work for more than 9 years in the Department of Nephrology of the National Institutes of Health (NIH) and has undergone clinical training in the Department of Nephrology, Mayo Clinic. In 2013, he returned to China through the introduction of American overseas talents from China Medical University. Major social part-time jobs: Standing Committee of the Kidney Pharmacology Subcommittee of the Chinese Pharmacological Society, Member of the Kidney Pathology Subcommittee of the China Non-Public Medical Association, and Member of the NIH Urine Protein Group Research Committee. At present, he has presided over 2 projects of the National Natural Science Foundation of China, and received 2.96 million research funds in four years. As a participant, he won the second prize of Science and Technology Progress Award of Liaoning Medical Association and the first prize of Shenyang Science and Technology Progress Award. He has published 33 SCI papers with a total impact factor of 143 points, which has been cited more than 2,000 times. Participated in the preparation of 3 English monographs, and a monograph on Chinese "Kidney Pharmacology". He has been a doctor for 26 years and is good at diagnosis and treatment of common diseases, frequently-occurring diseases and difficult diseases in this specialty. The research direction is the pathogenesis of lupus nephritis and new prevention and treatment methods. The international cooperation research project is a new diagnosis and treatment method for membranous nephropathy. Currently responsible for the Department of Nephrology membranous nephropathy.
References: Circular RNA expression alteration in exosomes from the brain extracellular space after traumatic brain injury in mice

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L-Glutamine CAS No.56-85-9

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