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通过与对照组相比,长链非编码 RNA“HOTAIR”/miRNA“206”/BDNF 网络在海洛因使用障碍患者血清中突触可塑性基因 arc 和 BDNF 水平表达改变中的潜在作用,通过 PI3K/AKT/mTOR 通路。

Potential role of the lncRNA "HOTAIR"/miRNA "206"/BDNF network in the alteration in expression of synaptic plasticity gene arc and BDNF level in sera of patients with heroin use disorder through the PI3K/AKT/mTOR pathway compared to the controls.

机构信息

Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Cairo University, Kasr Alainy Street, Cairo, 11562, Egypt.

Department of Biochemistry, Faculty of Medicine, Cairo University, Kasr Alainy Street, Cairo, 11562, Egypt.

出版信息

Mol Biol Rep. 2024 Feb 9;51(1):293. doi: 10.1007/s11033-024-09265-3.

DOI:10.1007/s11033-024-09265-3
PMID:38334898
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10858136/
Abstract

INTRODUCTION

Heroin use disorder (HUD) is a seriously increasing health issue, accounting for most deaths among drug abusers. Studying non-coding ribonucleic acid gene expression among drug abusers is a promising approach, as it may be used in diagnosis and therapeutics.

PARTICIPANTS AND METHODS

A total of 49 male heroin-dependent patients and 49 male control participants were recruited from Kasr Al Ainy Psychiatry and Addiction outpatient clinics, Faculty of Medicine, Cairo University. Sera were gathered. qRT-PCR was utilized for the detection of gene expression of non-coding RNAs such as "HOX transcript antisense RNA" (HOTAIR), micro-RNA (miRNA-206), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mechanistic target of rapamycin (mTOR), and Activity Regulated Cytoskeleton Associated Protein (Arc). Sera Brain-Derived Neurotrophic Factor (BDNF) levels were assessed using ELISA. Using a western blot made it possible to determine the protein expression of PI3K, AKT, and mTOR.

RESULTS

The study demonstrated that gene expressions of HOTAIR, AKT, PI3K, and Arc were considerably lowered between cases and controls, while gene expressions of miR-206 and mTOR1 were significantly raised. PI3K and AKT protein expressions were downregulated, while mTOR expressions were upregulated. BDNF levels were significantly decreased in some cases.

CONCLUSION

The results of this study suggest that decreased HOTAIR in HUD relieves miR-206 inhibition, which thus increases and affects downstream PI3K/AKT/mTOR, ARC, and BDNF expression. This may be shared in addictive and relapsing behaviors.

摘要

简介

海洛因使用障碍(HUD)是一个严重的健康问题,在药物滥用者中造成了大多数死亡。研究药物滥用者的非编码核糖核酸基因表达是一种很有前途的方法,因为它可能用于诊断和治疗。

参与者和方法

共招募了 49 名男性海洛因依赖患者和 49 名男性对照参与者,来自开罗大学医学院卡西勒阿因精神病学和成瘾门诊。收集血清。利用 qRT-PCR 检测非编码 RNA 基因表达,如“HOX 转录反义 RNA”(HOTAIR)、微 RNA(miRNA-206)、磷脂酰肌醇 3-激酶(PI3K)、蛋白激酶 B(AKT)、雷帕霉素的机械靶蛋白(mTOR)和活性调节细胞骨架相关蛋白(Arc)。使用 ELISA 评估血清脑源性神经营养因子(BDNF)水平。使用 Western blot 可以确定 PI3K、AKT 和 mTOR 的蛋白表达。

结果

研究表明,病例组和对照组之间 HOTAIR、AKT、PI3K 和 Arc 的基因表达显著降低,而 miR-206 和 mTOR1 的基因表达显著升高。PI3K 和 AKT 蛋白表达下调,而 mTOR 表达上调。BDNF 水平在某些情况下显著降低。

结论

本研究结果表明,HUD 中 HOTAIR 的减少缓解了 miR-206 的抑制,从而增加并影响下游的 PI3K/AKT/mTOR、ARC 和 BDNF 表达。这可能与成瘾和复发行为有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/e2788cb28d7d/11033_2024_9265_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/cfa8bc0975b3/11033_2024_9265_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/2ca4297074ff/11033_2024_9265_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/0241fab86863/11033_2024_9265_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/7eba32fbde08/11033_2024_9265_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/e2788cb28d7d/11033_2024_9265_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/cfa8bc0975b3/11033_2024_9265_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/2ca4297074ff/11033_2024_9265_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/0241fab86863/11033_2024_9265_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/7eba32fbde08/11033_2024_9265_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1b/10858136/e2788cb28d7d/11033_2024_9265_Fig5_HTML.jpg

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