Background: Lung adenocarcinoma (LUAD) is one of the most common and lethal cancer types worldwide. LINC0572 is a long non-coding RNA (lncRNA) that has been associated with the clinical characteristics of several types of malignancy. However, the biological mechanism of LINC0572 in LUAD is still unclear and remains to be elucidated.
Methods: R packages and online bioinformatic tools were used to investigate the biological characteristics of , including its abnormal expression, oncogenic role, and clinical prognostic value. and experiments were conducted to investigate the biological functions of in tumorigenesis and development. These included colony formation assays, cell migration assays, flow cytometry, cell counting kit-8 (CCK-8) cell proliferation and tumor transplant growth experiments.
Results: Bioinformatics results showed that was overexpressed in both LUAD and lung squamous cell carcinoma (LUSC) patients. overexpression was associated with shorter overall survival (OS) in LUAD. Further study of clinical specimens confirmed that was highly expressed in the tumor tissue of non-small cell lung cancer (NSCLC) patients. experiments also confirmed that was overexpressed in tumor cell lines. Inhibition of expression significantly impaired cell proliferation, cell migration, and clone formation. Experiments in nude mouse revealed that transplanted tumors with low expression of had significantly slower rates of growth in terms of volume and weight compared to the control group ( 0.05). In addition, gene set enrichment analysis (GSEA) and immune landscape profiling showed that can promote tumor initiation and progression by deregulating the cell cycle and immunocyte infiltration.
Conclusions: is overexpressed in tumor tissue relative to adjacent normal tissue. Moreover, LUAD patients with high expression of showed a worse survival prognosis. is associated with tumor initiation, progression and immune dysregulation. It therefore has potential value as a novel biomarker and therapeutic target in LUAD.
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http://dx.doi.org/10.31083/j.fbl2810257 | DOI Listing |
Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFBackground: There is an urgent need for new therapeutic and diagnostic targets for Alzheimer's disease (AD). Dementia afflicts roughly 55 million individuals worldwide, and the prevalence is increasing with longer lifespans and the absence of preventive therapies. Given the demonstrated heterogeneity of Alzheimer's disease in biological and genetic components, it is critical to identify new therapeutic approaches.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
View Article and Find Full Text PDFBackground: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.
Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.
Alzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
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