Let-7b-5p promotes cell apoptosis in Parkinson's disease by targeting HMGA2

Abstract

Parkinson's disease (PD), a common multi-Parkinson'sdiseasePD), commonmultifactorialneurodegenerativedisease, ischaracterizedby irreversiblelossof dopaminergicneuronsinthesubstantianigra. In-depth study of thepathogenesisof PD isof greatimportance. High-mobility group AT-hook 2 (HMGA2)hasbeenproposedtobeimplicatedwith neuronaldifferentiationandimpairmentof cognitivefunction. However, whetherHMGA2 playsaroleinPD israrely explored. Inthepresentstudy, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treatedPD micemodelsandN-methyl-4-phenylpyridinium(MPP+ )-treatedSH-SY5Y cellmodelswereestablished. Reversetranscription-quantitativePCR showedthatHMGA2 displayedlow levelsinbraintissuesof MPTP-treatedmiceandMPP+ -treatedSH-SY5Y cells. Moreover, HMGA2 overexpressionsuppressedSH-SY5Y cellapoptosis. Additionally, let-7b-5p boundwith HMGA2 3' untranslatedregion (UTR), anditsexpressionwasnegatively correlatedwith HMGA2 level. Moreover, let-7b-5p presentedhigh levelsinbraintissuesof PD miceandMPP+ -treatedSH-SY5Y cells, andknockdownof let-7b-5p inhibitedSH-SY5Y cellapoptosis. RescueassaysillustratedthatHMGA2 neutralizedthepromotiveeffectsof let-7b-5p mimicsonSH-SY5Y cellapoptosis. Inconclusion, thepresentstudy demonstratedthatlet-7b-5p contributestocellapoptosisinPD by targeting HMGA2, which offersapotentialtheoreticalbasisforthestudy of effectivetherapy in PD.