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.

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.