TY - JOUR AU - Asahchop, Eugene L. AU - Branton, William G. AU - Krishnan, Anand AU - Chen, Patricia A. AU - Yang, Dong AU - Kong, Linglong AU - Zochodne, Douglas W. AU - Brew, Bruce J. AU - Gill, M. John AU - Power, Christopher T1 - HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA–455-3p induction PY - 2018/12/06/ AB - Symptomatic distal sensory polyneuropathy (sDSP) is common and debilitating in people with HIV/AIDS, leading to neuropathic pain, although the condition’s cause is unknown. To investigate biomarkers and associated pathogenic mechanisms for sDSP, we examined plasma miRNA profiles in HIV/AIDS patients with sDSP or without sDSP in 2 independent cohorts together with assessing related pathogenic effects. Several miRNAs were found to be increased in the Discovery Cohort (sDSP, n = 29; non-DSP, n = 40) by array analyses and were increased in patients with sDSP compared with patients without sDSP. miR–455-3p displayed a 12-fold median increase in the sDSP group, which was confirmed by machine learning analyses and verified by reverse transcription PCR. In the Validation Cohort (sDSP n = 16, non-DSP n = 20, healthy controls n = 15), significant upregulation of miR–455-3p was also observed in the sDSP group. Bioinformatics revealed that miR–455-3p targeted multiple host genes implicated in peripheral nerve maintenance, including nerve growth factor (NGF) and related genes. Transfection of cultured human dorsal root ganglia with miR–455-3p showed a concentration-dependent reduction in neuronal β-III tubulin expression. Human neurons transfected with miR–455-3p demonstrated reduced neurite outgrowth and NGF expression that was reversed by anti–miR–455-3p antagomir cotreatment. miR–455-3p represents a potential biomarker for HIV-associated sDSP and might also exert pathogenic effects leading to sDSP. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.122450 VL - 3 IS - 23 UR - https://doi.org/10.1172/jci.insight.122450 PB - The American Society for Clinical Investigation ER -