パーキンソン病、小胞体ストレス、オートファジー経路に関連する相互マイクロRNAと標的遺伝子間の相互作用の解明:計算論的解析
Lakshmi Sankaranarayanan1, Jagan Muniyandi1, Yerragudi Saicharan Reddy1
1Degenerative Diseases and Phytotherapy Lab, Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry 605014, India.
Abstract:
MicroRNAs have been implicated in the pathophysiology of several diseases including Parkinson's disease (PD). Endoplasmic reticulum (ER) stress mediated unfolded protein response (UPR) pathway and autophagy play a vital role in preventing the accumulation of α-synuclein, which is one among the major causes of PD. This study presents data on the interactions among miRNAs and genes involved in PD, ER stress and autophagy pathways analysed using computational tools. When the interactions among selected 89 miRNAs and 44 genes were visualised using Cytoscape, three miRNAs- hsa-miR-34a-5p, hsa-miR-9-5p and hsa-miR-214-3p were selected as hub-miRNAs based on their degree of interaction. Further, functional annotation and functional interaction analyses were carried out for the target genes of these hub-miRNAs. Based on ontology and enrichment analyses data, the targets of miR-34a-5p and miR-9-5p such as BCL2, BECN1, ATG5, HMGB1, and ATG7 were observed to be involved in apoptosis and autophagy. Further, the functional interactions of ATG5-BECN1 and BECN1-HMGB1 emphasised their integrative roles in autophagy. On the other hand, the targets of miR-214-3b such as XBP1, ATF4, BCL2L11, and BAX were found to be associated with ER stress and apoptosis. Also, functional interactions observed between XBP1-ATF4, ATF4-BCL2L11, and BCL2L11-BAX highlighted their integrative roles in neuronal apoptosis and ER stress pathways. Overall findings indicated that dysfunctions of these miRNAs might contribute to neuronal apoptosis through their regulatory roles in autophagy and ER stress pathways.
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