Epigenetic transcripts of LINC01311 and hsa‐miR‐146a‐5p regulate neural development in a cellular model of Alzheimer's disease

Abstract

Emerging evidence has shown that Long noncoding RNAs (LncRNAs) are aberrantly expressed and functionally involved in the development of neurodegenerative disorders. In this work, we investigated the regulatory effects of lncRNA of LINC01311 and its competing endogenous RNA target of hsa‐miR‐146a‐5p in a cellular model of Alzheimer's disease (AD). SH‐SY5Y cells were treated with synthetic Βeta‐Amyloid Peptide (1‐42) (AB1‐42) in vitro to induce AD‐like neural injuries. Expressions of LINC01311 and hsa‐miR‐146a‐5p were monitored by qRT‐PCR. LINC01311 was upregulated and hsa‐miR‐146a‐5p downregulated to examine their functional regulations on AB1‐42‐induced apoptosis, proliferation slowdown, autophagy, and amyloid precursor protein (APP) accumulations. Hsa‐miR‐146a‐5p was also overexpressed in LINC01311‐upregulated SH‐SY5Y cells to examine their correlated regulations on AB1‐42‐induced neural injuries. LINC01311 was downregulated whereas hsa‐miR‐146a‐5p upregulated in AB1‐42 treated SH‐SY5Y cells. LINC01311 upregulation and hsa‐miR‐146a‐5p downregulation protected AB1‐42‐induced apoptosis, proliferation slowdown, autophagy, and APP accumulations in SH‐SY5Y cells. Hsa‐miR‐146a‐5p overexpression reversed the protection of LINC01311 on AB1‐42‐induced neural injuries. Our work demonstrated that the epigenetic axis of LINC01311/hsa‐miR‐146a‐5p was involved in the functional regulation of human‐lineage neurons in a cellular model of AD, thus suggesting a clinical potential of exploring epigenetic network for treating AD patients.

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

“…Further experiments showed that LINC01311 promotes proliferation and reduces apoptosis and autophagy by sponging miR-146a-5p (Table S1). Consistent with these findings, upregulation of this miRNA was observed in AD patients and AD animals [91].…”

Molecular Insight Into the Therapeutic Potential of Long Non-coding RNA-Associated Competing Endogenous RNA Axes in Alzheimer’s Disease: A Systematic Scoping Review

“…The full texts of the remaining 34 articles were evaluated, and 20 more articles were also excluded because they did not validate the components of the ceRNA loop using molecular techniques ( Wang et al, 2017 ; Yu et al, 2018 ; Zhou et al, 2019 ; Ma et al, 2020 ; Xu and Jia, 2020 ; Huaying et al, 2021 ; Lu et al, 2021 ; Ou et al, 2021 ; Tang et al, 2021 ; Zhang et al, 2021 ) and did not use human specimens or cell lines ( Jiang et al, 2016 ; Cai et al, 2017 ; Wang J. et al, 2018 ; Wang X. et al, 2018 ; Ma P. et al, 2019 ; Zhao et al, 2019 ; Li L. et al, 2020 ; Li X. et al, 2020 ; Yue et al, 2020 ; Zhou et al, 2020 ). Lastly, a total of 14 eligible articles remained ( Faghihi et al, 2010 ; Ke et al, 2019 ; Wang et al, 2019 ; Zeng et al, 2019 ; Zhu et al, 2019 ; Gao et al, 2020 ; Ge et al, 2020 ; Gu et al, 2020 , 2021 ; He W. et al, 2020 ; Yan et al, 2020 ; Yue et al, 2020 ; Fan et al, 2021 ; Zhang and Wang, 2021 ).…”

“…All but one study ( Faghihi et al, 2010 ) was conducted in China. Eleven studies examined the ceRNA regulatory loop on human cell lines ( Ke et al, 2019 ; Wang et al, 2019 ; Zeng et al, 2019 ; Zhu et al, 2019 ; Gao et al, 2020 ; Ge et al, 2020 ; Gu et al, 2020 , 2021 ; Yan et al, 2020 ; Yue et al, 2020 ; Fan et al, 2021 ) and three on both human specimens and cell lines ( Faghihi et al, 2010 ; He W. et al, 2020 ; Zhang and Wang, 2021 ). All studies with human specimens had a case-control design.…”

“…The lncRNA small nucleolar RNA host gene 1 ( SNHG1 ) ( Wang et al, 2019 ; Gao et al, 2020 ) and the lncRNA ribonuclease P RNA component H1 ( RPPH1 ) ( Gu et al, 2020 , 2021 ) were each reported in two articles. The remaining ceRNAs were reported once each in six studies ( Ke et al, 2019 ; Zhu et al, 2019 ; Yan et al, 2020 ; Yue et al, 2020 ; Fan et al, 2021 ; Zhang and Wang, 2021 ). Among the identified miRNAs, miR-107 was reported in three regulatory axes in three different studies ( Ke et al, 2019 ; Zeng et al, 2019 ; Yue et al, 2020 ).…”

“…It was reported that the LINC01311 / hsa-miR-146a-5p axis could operate as a functional regulator in AB1-42-stimulated apoptosis, proliferation slowdown, autophagy, and accumulated APP in human-lineage neurons ( Fan et al, 2021 ). As a new lncRNA, LINC01311 was discovered throughout human genome-wide screening, which has an aberrant expression in human liver and prostate cancers ( Zhu et al, 2016 ; Imada et al, 2020 ).…”