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LncRNA ENST00000440246.1 Promotes Alzheimer’s Disease Progression by Targeting PP2A

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Abstract

Alzheimer’s disease (AD) is an extremely prevalent neurodegenerative disease. Long noncoding RNAs (lncRNAs) play pivotal roles in the regulation of AD. However, the function of most lncRNAs in AD remains to be elucidated. In this study, the effects of lncRNA ENST00000440246.1 on the biological characteristics of AD were explored. Differentially expressed lncRNAs in AD were identified through bioinformatics analysis and peripheral blood from thirty AD patients was collected to verify the expression of these lncRNAs by quantitative real-time polymerase chain reaction (RT-qPCR). The correlations between lncRNAs and the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) were assessed by Pearson’s correlation analysis. Immunofluorescence (IF), Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted to evaluate the biological effect of ENST00000440246.1 and protein phosphatase 2 A (PP2A) in SK-N-SH cells. Gene expression at the protein and mRNA levels was analyzed by Western blotting and RT-qPCR. The interaction between PP2A and ENST00000440246.1 was confirmed by IntaRNA and RNA pulldown assays. ENST00000440246.1 was upregulated and significantly negatively correlated with the MMSE and MoCA scores and the overexpression of ENST00000440246.1 inhibited cell proliferation and facilitated apoptosis and Aβ expression in SK-N-SH cells. Mechanistically, ENST00000440246.1 targeted PP2A and regulated AD-related gene expression. The silencing of ENST00000440246.1 had the opposite effect. Furthermore, PP2A overexpression reversed the influence of ENST00000440246.1 overexpression in SK-N-SH cells. In conclusion, ENST00000440246.1 could promote AD progression by targeting PP2A, which indicates that ENST00000440246.1 has the potential to be a diagnostic target in AD.

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Data Availability

The datasets analysed during the current study are available in the GEO (https://www.ncbi.nlm.nih.gov/geo/).

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Funding

This study was supported by The Major Science and Technology Project of Anhui Province (No.201903a07020016) and The University Synergy Innovation Program of Anhui Province (No.GXXT-2020-025).

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Authors and Affiliations

  1. Experimental Center of Clinical Research, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, Anhui, China

    Shang Gao, Chang Fan & Hui Jiang

  2. Key Laboratory of Xin’an Medicine of the Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230031, Anhui, China

    Yongzhong Wang, Wenming Yang & Hui Jiang

  3. Encephalopathy Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, Anhui, China

    Wenming Yang

  4. Department of pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, Anhui, China

    Yongzhong Wang

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  1. Shang Gao
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  2. Chang Fan
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  3. Yongzhong Wang
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  4. Wenming Yang
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  5. Hui Jiang
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Contributions

GS, JH, and YWM conceived and designed the experiments. JH and YWM collected samples and clinical data. GS and FC performed the laboratory experiments. GS, FC and WYZ analyzed the clinical and molecular data. GS and JH contributed reagents/materials/analysis tools. GS wrote the paper. All authors critically revised and approved it for publication.

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Correspondence to Wenming Yang or Hui Jiang.

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Conflict of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Ethics Approval

The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui University of Chinese Medicine (approval no. 2022AH-01) and conducted according to the Declaration of Helsinki’s guidelines. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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Gao, S., Fan, C., Wang, Y. et al. LncRNA ENST00000440246.1 Promotes Alzheimer’s Disease Progression by Targeting PP2A. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10552-0

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