Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disease. Recent studies employing microRNA-seq and genome-wide sequencing have identified some non-coding RNAs that are influentially involved in AD pathogenesis. Non-coding RNAs can compete with other endogenous RNAs by microRNA response elements (MREs) and manipulate biological processes, such as tumorigenesis. However, only a few non-coding RNAs have been reported in the pathogenesis of AD. In this study, we constructed the first competing endogenous RNA (ceRNA) network leveraging whole transcriptome sequencing and a previously studied microRNA-seq of APPswe/PS1ΔE9 transgenic mice. The underlying mechanisms for the involvement of ceRNA in AD were validated using the Dual Luciferase Reporter Assay, detection of transcription levels by quantitative RT-PCR and translation levels by Western blotting, and morphological examination in primary cultured neurons. In the ceRNA network, four lncRNAs (C030034L19Rik, Rpph1, A830012C17Rik, and Gm15477) and five miRNAs (miR-182-5p, miR-330-5p, miR-326-3p, miR-132-3p, and miR-484) are enriched in nine pathways and an AD-related gene pool. Among them, Ribonuclease P RNA component H1 (Rpph1) is upregulated in the cortex of APPswe/PS1ΔE9 mice compared to wild type controls. Rpph1 binds to miR326-3p/miR-330-5p and causes the release of their downstream target Cdc42, which leads to CDC42 upregulation. This effect was disrupted upon mutation of the MRE on Rpph1. Moreover, overexpression of Rpph1 increased dendritic spine density in primary cultured hippocampal pyramidal neurons, whereas knocking down of Rpph1 had the reverse effect. In conclusion, Rpph1 modulates CDC42 expression level in a ceRNA-dependent manner, which may represent a compensatory mechanism in the early stage of the AD pathogenesis.

Human papillomavirus viral load level is positively associated with cervical lesion grade. Ten relative light units/control or greater is a viable threshold for immediate colposcopy whereas 1 or greater or less than 10 RLU/CO is advised to reflex cytology for optimizing sensitivity and specificity, as well as referral rates.

Alzheimer’s disease (AD) is the most common cause of dementia. Amyloid β (Abeta, Aβ) deposition and intracellular tangles are the pathological hallmarks of AD. MicroRNAs (miRNAs) are small non-coding RNAs, which have been found to play very important roles, and have the potential to serve as diagnostic markers during neuronal pathogenesis. In this study, we aimed to determine the roles of miR-99b-5p and miR-100-5p in Aβ-induced neuronal pathologies. We detected the expression levels of miR-99b-5p and miR-100-5p in the brains of APPswe/PS1ΔE9 double-transgenic mice (APP/PS1 mice) at different age stages and found that both miRNAs were decreased at early stages while increased at late stages of APP/PS1 mice when compared with the age-matched wild type (WT) mice. Similar phenomenon was also observed in Aβ-treated cultured cells. We also confirmed that mammalian target of rapamycin (mTOR) is one of the targets of miR-99b-5p/100-5p, which is consistent with previous studies in cancer. MiR-99b-5p/100-5p has been found to promote cell apoptosis with the Aβ treatment. This effect may be induced via the mTOR pathway. In our study, we find both miR-99b-5p and miR-100-5p affect neuron survival by targeting mTOR. We also speculate that dynamic change of miR-99b-5p/100-5p levels during Aβ-associated pathologies might be attributed to Aβ-induced endoplasmic reticulum stress (ER stress), suggesting the potential role of the “ER stress–miRNAs–mTOR” axis in Aβ-related AD pathogenesis.