Alzheimer’s disease (AD) is a neurodegenerative disease that primarily affects the elderly population and is the leading cause of dementia. Meanwhile, the vascular hypothesis suggests that vascular damage occurs in the early stages of the disease, leading to neurodegeneration and hindered waste clearance, which in turn triggers a series of events including the accumulation of amyloid plaques and Tau protein tangles. Non-coding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), have been found to be involved in the regulation of AD. Furthermore, lncRNAs and circRNAs can act as competitive endogenous RNAs to inhibit miRNAs, and their interactions can form a complex regulatory network. Exosomes, which are extracellular vesicles (EVs), are believed to be able to transfer ncRNAs between cells, thus playing a regulatory role in the brain by crossing the blood-brain barrier (BBB). Exosomes are part of the intercellular carrier system; therefore, utilizing exosomes to deliver drugs to recipient cells might not activate the immune system, making it a potential strategy to treat central nervous system diseases. In this review, we review that AD is a multifactorial neurological disease and that ncRNAs can regulate its multiple pathogenic mechanisms to improve our understanding of the etiology of AD and to simultaneously regulate multiple pathogenic mechanisms of AD through the binding of ncRNAs to exosomes to improve the treatment of AD.

Purpose: As a novel genetic biomarker, little information is available about the possible role of SPINDOC in different malignant tumors and in hepatocellular carcinoma (HCC). Methods: Based on The Cancer Genome Atlas (TCGA) database, the expression level of SPINDOC in pan-cancer and hepatocellular carcinoma samples was first determined using bioinformatics analysis. The potential relationship between the expression level as well as the clinical characteristics and the molecular mechanisms through which SPINDOC can promote the proliferation, invasion and migration of HCC cells was evaluated. In addition, cell-based studies and in vivo experiments were used to verify the bioinformatics analysis results. Results: Bioinformatics analysis showed that SPINDOC expression was significantly increased in 18 human malignancies and the gene expression level was positively correlated with poor clinical prognosis in kidney renal papillary cell carcinoma (KIRP), pheochromocytoma and paraganglioma (PCPG) and liver hepatocellular carcinoma (LIHC). The main type of genetic variation of SPINDOC was amplification, and the increase of SPINDOC mRNA expression level was directly related to the amplification of this gene. The expression level of SPINDOC in patients with primary HCC was positively correlated with poor clinical prognosis, as well as the clinical grade and stage of carcinoma. Gene set enrichment analysis (GSEA) analysis showed that high expression of SPINDOC could activate Wnt/β-catenin signaling pathway. Moreover, in vitro and in vivo experiments showed that SPINDOC gene silencing significantly inhibited the proliferation, migration and invasion of Huh7 and SK-HEP-1 cells and decreased the expression of SPIN1, Wnt1, β-catenin and cyclin D1 but increased the expression of AXIN2. Conclusion: SPINDOC is highly expressed in pan-cancer and HCC samples. This factor can effectively promote the invasion and migration of hepatocellular carcinoma (HCC) cells by activating Wnt/β-catenin signaling pathway, and thus can serve as a potential therapeutic target for HCC management.

Background: Hepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses.Methods: scRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC.Results: These analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results.Conclusion: These results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.

As a novel genetic biomarker, the potential role of SH3D21 in hepatocellular carcinoma remains unclear. Here, we decipher the expression and function of SH3D21 in human hepatocellular carcinoma. The expression level and clinical significance of SH3D21 in hepatocellular carcinoma patients, the relationship between SH3D21 and the features of tumor microenvironment (TME) and role of SH3D21 in promoting hepatocellular carcinoma progression were analyzed based on the bulk samples obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Single-cell sequencing samples from Gene Expression Omnibus (GEO) database were employed to verify the prediction mechanism. Additionally, different biological effects of SH3D21 on hepatocellular carcinoma cells were investigated by qRT-PCR, CCK-8 assay, colony forming assay and Western blot analysis. Bioinformatics analysis and in vitro experiments revealed that the expression level of SH3D21 was up-regulated in hepatocellular carcinoma and correlated with the poor prognosis in hepatocellular carcinoma patients. SH3D21 effectively promoted the proliferation, invasion, and migration as well as the formation of immunosuppressive microenvironment of hepatocellular carcinoma. In addition, SH3D21 can activate the PI3K/AKT/mTOR signaling pathway. SH3D21 stimulates the progression of hepatocellular carcinoma by activating the PI3K/AKT/mTOR signaling pathway, and SH3D21 can serve as a prognostic biomarker and therapeutic target for hepatocellular carcinoma.