Identification of the Genome-wide Expression Patterns of Long Non-coding RNAs and mRNAs in Mice with Streptozotocin-induced Diabetic Neuropathic Pain

Neuroscience. 2019 Mar 15:402:90-103. doi: 10.1016/j.neuroscience.2018.12.040. Epub 2018 Dec 29.

Abstract

Diabetic neuropathic pain (DNP), an early symptom of diabetic neuropathy, involves complex mechanisms. Long non-coding RNA (lncRNA) dysregulation contributes to the pathogenesis of various human diseases. Here, we investigated the genome-wide expression patterns of lncRNAs and genes in the spinal dorsal horn of mice with streptozotocin-induced DNP. Microarray analysis identified 1481 differentially expressed (DE) lncRNAs and 1096 DE mRNAs in DNP mice. Functional analysis showed that transforming growth factor-beta receptor binding was the most significant molecular function and retrograde endocannabinoid signaling was the most significant pathway of DE mRNAs. Calcium ion transport was the second most significant biological process of DE lncRNAs. Finally, we found 289 neighboring and 57 overlapping lncRNA-mRNA pairs, including ENSMUST00000150952-Mbp and AK081017-Usp15, which may be involved in DNP pathogenesis. Microarray data were validated through quantitative PCR of selected lncRNAs and mRNAs. These results suggest that aberrant expression of lncRNAs may contribute to the pathogenesis of DNP.

Keywords: diabetic neuropathic pain (DNP); genome-wide expression; long non-coding RNAs (lncRNAs); microarray; spinal dorsal horn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetic Neuropathies / chemically induced
  • Diabetic Neuropathies / genetics
  • Diabetic Neuropathies / metabolism*
  • Endocannabinoids / genetics
  • Endocannabinoids / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Male
  • Mice, Inbred BALB C
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Signal Transduction
  • Spinal Cord Dorsal Horn / metabolism*
  • Streptozocin / administration & dosage

Substances

  • Endocannabinoids
  • RNA, Long Noncoding
  • RNA, Messenger
  • Streptozocin