Long noncoding RNA HAGLROS regulates apoptosis and autophagy in Parkinson's disease via regulating miR-100/ATG10 axis and PI3K/Akt/mTOR pathway activation.

Parkinson's disease (PD) is a common age-related neurodegenerative disease resulted from the progressive degeneration of dopaminergic neurons in the pars compacta region of substantia nigra. The goal of this study was to investigate the effects and mechanisms of long noncoding RNA (lncRNA) on the apoptosis and autophagy in PD. The MPTP-induced PD mouse model and MPP⁺-intoxicated SH-SY5Y cell model were established, and the expression levels of HAGLduanyu1670 and miR-100 were determined. Subsequently, the effects of suppression of HAGLduanyu1670 on apoptosis and autophagy in MPTP-induced PD mouse model and in MPP⁺-intoxicated SH-SY5Y cells were investigated. In addition, the association between HAGLduanyu1670 and miR-100 as well as HAGLduanyu1670 and activation of phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in MPP⁺-intoxicated SH-SY5Y cells was explored. HAGLduanyu1670 was increasingly expressed in MPTP-induced PD mouse model and MPP⁺-intoxicated SH-SY5Y cells and suppression of HAGLRO decreased apoptosis and autophagy in both in vivo and in vitro PD models. Further in vitro studies showed that HAGLRO negatively regulated miR-100 expression, and HAGLduanyu1670 regulated apoptosis and autophagy of MPP⁺-intoxicated SH-SY5Y cells through sponging miR-100. Moreover, ATG10 was identified as a target of miR-100. Besides, suppression of HAGLduanyu1670 alleviated MPP⁺-intoxicated SH-SY5Y cell injury by activating PI3K/AKT/mTOR pathway. Our findings reveal that upregulation of HAGLduanyu1670 may contribute to the development of PD via inhibiting apoptosis and autophagy, which may be achieved by regulating miR-100/ATG10 axis and PI3K/AKT/mTOR pathway activation.

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