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链脲佐菌素诱导的糖尿病性神经病理性疼痛通过测序分析确定改变了小鼠脊髓中非编码RNA的表达谱。

Diabetic neuropathic pain induced by streptozotocin alters the expression profile of non-coding RNAs in the spinal cord of mice as determined by sequencing analysis.

作者信息

He Jian, Wang Han Bin, Huang Jiang Ju, Zhang Lei, Li Dong Lin, He Wan You, Xiong Qing Ming, Qin Zai Sheng

机构信息

Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510000, P.R. China.

Department of Anesthesiology, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China.

出版信息

Exp Ther Med. 2021 Jul;22(1):775. doi: 10.3892/etm.2021.10207. Epub 2021 May 18.

Abstract

Diabetic neuropathic pain (DNP) is one of the most serious complications of diabetes. Patients with DNP always exhibit spontaneous and stimulus-evoked pain. However, the pathogenesis of DNP remains to be fully elucidated. Non-coding RNAs (ncRNAs) serve important roles in several cellular processes and dysregulated expression may result in the development of several diseases, including DNP. Although ncRNAs have been suggested to be involved in the pathogenesis of DNP, their precise roles remain to be determined. In the present study, sequencing analysis was used to investigate the expression patterns of coding genes, microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs) in the spinal cord of mice with streptozotocin (STZ)-induced DNP. A total of 30 mRNAs, 148 miRNAs, 9 lncRNAs and 135 circRNAs exhibited significantly dysregulated expression 42 days after STZ injection. Functional enrichment analysis indicated that protein digestion and absorption pathways were the most significantly affected pathways of the differentially expressed (DE) mRNAs. The Rap1 signaling pathway, human T-lymphotropic virus-I infection and the MAPK signaling pathway were the three most significant pathways of the DE miRNAs. A total of 2,118 distinct circRNAs were identified and the length of the majority of the circRNAs was <1,000 nucleotides (nt) (1,552 circRNAs were >1,000 nt) with a median length of 620 nt. In the present study, the expression characteristics of coding genes, miRNAs, lncRNAs and circRNAs in DNP mice were determined; it paves the road for further studies on the mechanisms associated with DNP and potentially facilitates the discovery of novel ncRNAs for therapeutic targeting in the management of DNP.

摘要

糖尿病性神经病理性疼痛(DNP)是糖尿病最严重的并发症之一。DNP患者总是表现出自发性疼痛和刺激诱发的疼痛。然而,DNP的发病机制仍有待充分阐明。非编码RNA(ncRNAs)在多个细胞过程中发挥重要作用,其表达失调可能导致包括DNP在内的多种疾病的发生。尽管已有研究表明ncRNAs参与了DNP的发病机制,但其确切作用仍有待确定。在本研究中,采用测序分析来研究链脲佐菌素(STZ)诱导的DNP小鼠脊髓中编码基因、微小RNA(miRNAs)、长链非编码RNA(lncRNAs)和环状RNA(circRNAs)的表达模式。在STZ注射后42天,共有30种mRNA、148种miRNA、9种lncRNA和135种circRNA表现出明显的表达失调。功能富集分析表明,蛋白质消化和吸收途径是差异表达(DE)mRNA中受影响最显著的途径。Rap1信号通路、人类嗜T淋巴细胞病毒I感染和丝裂原活化蛋白激酶(MAPK)信号通路是DE miRNA中最显著的三条途径。共鉴定出2118种不同的circRNA,大多数circRNA的长度<1000个核苷酸(nt)(1552种circRNA>1000 nt),中位数长度为620 nt。在本研究中,确定了DNP小鼠中编码基因、miRNA、lncRNA和circRNA的表达特征;这为进一步研究DNP相关机制铺平了道路,并可能有助于发现用于DNP治疗靶点的新型ncRNAs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ec/8145263/7c6df3b4809e/etm-22-01-10207-g00.jpg

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