MicroRNA-296-5p is differentially expressed in individuals with and without HIV-1 infection

Abstract MicroRNAs are considered as potential biomarkers, agents, or therapeutic targets; few studies have addressed the expression of miRNAs in treatment-naïve patients infected with HIV-1. The aim of this study was to assess plasma relative circulating miRNA expression profiles in treatment-naïve Mexican patients with HIV/AIDS and healthy individuals using a commercial array. A low CD4+ T cell count and high viral load were found in all patients. Decreased relative miRNA-296-5p expression was observed in patients; moreover, this was the only miRNA that showed differences between the two groups. Thus, we measured the absolute expression of miR-296-5p by qPCR, confirming the result with statistically significant differences (P < 0.05). There is evidence that miR-296-5p regulates the expression of the PIN1 gene, which encodes the peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1, that is involved in different stages of the biological cycle of HIV-1, this relationship is corroborated by bioinformatics analysis and ELISA assay was used to measure plasma levels of PIN1. The decreased expression of miR-296-5p found in naïve patients with HIV infection suggests a regulatory activity of this miRNA on virus replication, making it a potential therapeutic agent against HIV. Finally, miR-296-5p could be inhibiting the virus transcription by regulating genes different than PIN1.

摘要 微RNA（microRNAs，miRNAs）被视为潜在的生物标志物、治疗制剂或治疗靶点；目前鲜有研究探讨未经抗反转录病毒治疗的HIV-1感染者体内miRNA的表达情况。本研究旨在通过商业化芯片技术，分析未经治疗的墨西哥HIV/AIDS患者与健康个体的血浆循环miRNA相对表达谱。所有受试患者均表现为CD4+ T细胞计数降低、病毒载量升高。研究观察到患者体内miR-296-5p的相对表达量下调，且该miRNA是两组间唯一存在表达差异的miRNA。据此，我们通过qPCR（实时定量聚合酶链反应）检测了miR-296-5p的绝对表达量，证实该差异具有统计学意义（P < 0.05）。已有研究表明，miR-296-5p可调控PIN1基因的表达，该基因编码肽酰脯氨酰顺反异构酶NIMA相互作用蛋白1（peptidylprolyl Cis/Trans isomerase NIMA-Interacting-1），而该蛋白参与HIV-1生物学周期的多个阶段；我们通过生物信息学分析证实了这一调控关系，并采用ELISA（酶联免疫吸附试验）检测血浆中PIN1的蛋白水平。HIV感染未经治疗患者体内miR-296-5p表达下调，提示该miRNA可对病毒复制发挥调控活性，使其成为抗HIV的潜在治疗制剂。此外，miR-296-5p或可通过调控除PIN1以外的其他基因抑制病毒转录。