Abstract:Resistant depression (TED) is the most common mental illness (Sowa-Kućma et al., 2018). About 350 million patients have become a serious public health problem all over the world (Cusin et al., 2017). Studies have shown that TED is also associated with other diseases, such as osteoporosis, diabetes, and cerebral ischemia (Grønli & Wynn, 2013; Nierenberg, Mcintyre, & Sachs, 2015). Even so, the researchers' understanding of depression is still very limited. In recent years, people have found the structural change… Show more
“…Interestingly, we found that this specific region of circCARHSP1 is targeted by miR-24-3p and miR-345-5p. Notably, miR-24-3p regulates neuronal differentiation and promotes neurite growth [ 75 , 76 ], while miR-345-5p controls viability of microglia cells and represents a promising biomarker of the progression of C9orf72-associated disease [ 77 , 78 ].…”
Deregulation of RNA metabolism has emerged as one of the key events leading to the degeneration of motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or on proteins involved in aspects of RNA metabolism account for the majority of familiar forms of ALS. In particular, the impact of the ALS-linked mutations of the RBP FUS on many aspects of RNA-related processes has been vastly investigated. FUS plays a pivotal role in splicing regulation and its mutations severely alter the exon composition of transcripts coding for proteins involved in neurogenesis, axon guidance, and synaptic activity. In this study, by using in vitro-derived human MNs, we investigate the effect of the P525L FUS mutation on non-canonical splicing events that leads to the formation of circular RNAs (circRNAs). We observed altered levels of circRNAs in FUSP525L MNs and a preferential binding of the mutant protein to introns flanking downregulated circRNAs and containing inverted Alu repeats. For a subset of circRNAs, FUSP525L also impacts their nuclear/cytoplasmic partitioning, confirming its involvement in different processes of RNA metabolism. Finally, we assess the potential of cytoplasmic circRNAs to act as miRNA sponges, with possible implications in ALS pathogenesis.
“…Interestingly, we found that this specific region of circCARHSP1 is targeted by miR-24-3p and miR-345-5p. Notably, miR-24-3p regulates neuronal differentiation and promotes neurite growth [ 75 , 76 ], while miR-345-5p controls viability of microglia cells and represents a promising biomarker of the progression of C9orf72-associated disease [ 77 , 78 ].…”
Deregulation of RNA metabolism has emerged as one of the key events leading to the degeneration of motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or on proteins involved in aspects of RNA metabolism account for the majority of familiar forms of ALS. In particular, the impact of the ALS-linked mutations of the RBP FUS on many aspects of RNA-related processes has been vastly investigated. FUS plays a pivotal role in splicing regulation and its mutations severely alter the exon composition of transcripts coding for proteins involved in neurogenesis, axon guidance, and synaptic activity. In this study, by using in vitro-derived human MNs, we investigate the effect of the P525L FUS mutation on non-canonical splicing events that leads to the formation of circular RNAs (circRNAs). We observed altered levels of circRNAs in FUSP525L MNs and a preferential binding of the mutant protein to introns flanking downregulated circRNAs and containing inverted Alu repeats. For a subset of circRNAs, FUSP525L also impacts their nuclear/cytoplasmic partitioning, confirming its involvement in different processes of RNA metabolism. Finally, we assess the potential of cytoplasmic circRNAs to act as miRNA sponges, with possible implications in ALS pathogenesis.
“…The apoptosis of microglia was evaluated using an Annexin V-FITC/PI apoptosis detection kit (BD Biosciences, CA, USA) via flow cytometry analysis [ 38 ]. After washed with phosphate buffered saline, microglial cells with indicate treatments were resuspended in binding buffer and then stained with Annexin V-FITC (5 µL; 10 min) and propidium iodide (PI) (5 µL; 5 min) at room temperature in the darkness according to the manufacturer’s instructions.…”
Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Multiple reports have elucidated that microRNAs are promising biomarkers for AD diagnosis and treatment. Herein, the effect of miR-191-5p on microglial cell injury and the underlying mechanism were explored. APP/PS1 transgenic mice were utilized to establish mouse model of AD. Amyloid-β protein 1–42 (Aβ1-42)-treated microglia were applied to establish
in vitro
cell model of AD. MiR-191-5p expression in hippocampus and microglia was measured by reverse transcription quantitative polymerase chain reaction. The viability and apoptosis of microglia were evaluated by Cell Counting Kit-8 assays and flow cytometry analyses, respectively. The binding relationship between miR-191-5p and its downstream target mitogen-activated protein kinase kinase kinase 12 (Map3k12) was determined by luciferase reporter assays. Pathological degeneration of hippocampus was tested using hematoxylin-eosin staining and Nissl staining. Aβ expression in hippocampus was examined via immunohistochemistry. In this study, miR-191-5p was downregulated in Aβ1-42-stimulated microglia and hippocampal tissues of APP/PS1 mice. MiR-191-5p overexpression facilitated cell viability and inhibited apoptosis rate of Aβ1-42-treated microglia. Mechanically, miR-191-5p targeted Map3k12 3ʹ-untranslated region to downregulate Map3k12 expression. MiR-191-5p inhibited Aβ1-42-induced microglial cell injury and inactivated the MAPK signaling by downregulating Map3k12. Overall, miR-191-5p alleviated Aβ1-42-induced microglia cell injury by targeting Map3k12 to inhibit the MAPK signaling pathway in microglia.
“…miR-345-5p is a tumor-suppressive miRNA in pancreatic cancer progression [38]. miR-345-5p induces inflammatory damage in hippocampal neurons [39] and has oncogenic roles [40]. miR-345-5p is also a promising blood-derived disease biomarker in multiple sclerosis [41].…”
Section: Lmcd1-as1 In Cholangiocarcinomamentioning
Long noncoding RNAs (lncRNAs) are one of the interesting fields in cancer researches. LncRNAs are generally dysregulated in many diseases. LMCD1 antisense RNA 1 (LMCD1-AS1) is a newly identified lncRNA with protumorigenic functions on tumor cells. LMCD1-AS1 expression is increased in hepatocellular carcinoma (HCC). LMCD1-AS1 is a sponge of miR-106b-5p activity. LMCD1-AS1 modulates the survival of osteosarcoma via targeting miR-106b-5p. LMCD1-AS1 and Sp1 are highly expressed in osteosarcoma. SP1 can bind to the promoter region of LMCD1-AS1, resulting in its overexpression in osteosarcoma. GLI2 is shown to bind to the LMCD1-AS1 promoter and is transcriptionally activated by LMCD1-AS1. LMCD1 acts as a miR-1287-5p sponge to increase GLI2 expression. LMCD1 is abundantly expressed in kidney tissue. Moreover, it is functionally involved in protein-protein interactions with transcriptional co-repressor activity, including regulation of the calcineurin-NFAT signaling cascade known to play a critical role in recovery from acute kidney injury (AKI). The E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis is a newly identified regulatory mechanism, which has a function in cholangiocarcinoma (CCA) tumorigenesis and progression and provides potential therapeutic targets for CCA. Also, LMCD1-AS1 functions in thyroid cancer (THCA) development. LMCD1-AS1 is overexpressed in THCA cells, and LMCD1-AS1 knockdown suppresses the malignant phenotypes of THCA cells. In THCA development, LMCD1-AS1 exerts protumorigenic function through sponging miR-1287-5p to increase GLI2 expression, constituting a feedback loop of LMCD1-AS1/miR-1287-5p/ GLI2. In this review, the author focuses on the molecular mechanisms of newly identified long noncoding RNA LMCD1 antisense RNA 1 (LMCD1-AS1). Anti-Cancer Drugs
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