Prognostic and clinicopathologic significance of MicroRNA-125a-5p in cancers

Ye, Haidong; Zhu, Wei; Mei, Lina; Lu, Zhouxiang

doi:10.1097/md.0000000000016685

Cited by 6 publications

(4 citation statements)

References 30 publications

(28 reference statements)

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“…From the panel of identified microRNAs, the one showing a significant survival association with the greatest number of cancers was hsa-miR-125-5p. The pattern was primarily for high expression of hsa-miR-125-5p to be good for patient outcomes (in pancreatic cancer, lung cancer, renal cancer, bladder cancer, and mesothelioma) which is in agreement with a recent metanalysis of patient data [ 33 ]. The mechanistic understanding of this effect is supported by a body of evidence that shows that hsa-miR-125-5p acts as a tumor suppressor in a variety of cancers.…”

Section: Discussionsupporting

confidence: 85%

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study

Kannan

O’Connor

Bakker

2021

IJMS

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Immune checkpoint blockade targeting PD-1 (PDCD1)/PD-L1 (CD274) is increasingly used for multiple cancers. However, efficacy and adverse-related events vary significantly. This bioinformatic study interrogated molecular differences pertaining to PDCD1/CD274 and their correlated genes on a pan-cancer basis to identify differences between cancer types. Patient RNA-seq data from fifteen cancer types were accessed on cBioPortal to determine the role of PDCD1/CD274 in patient survival and to identify positively and negatively correlated genes, which were also assessed for clinical relevance. Genes correlating with PDCD1/CD274 across multiple cancers were taken forward for drug repurposing via DRUGSURV and microRNA analysis using miRDB and miRabel. MicroRNAs were also screened for clinical relevance using OncomiR. Forty genes were consistently correlated with PDCD1/CD274 across multiple cancers, with the cancers themselves exhibiting a differential role for the correlated genes in terms of patient survival. Esophageal and renal cancers in particular stood out in this regard as having a unique survival profile. Forty-nine putative microRNAs were identified as being linked to the PDCD1/CD274 network, which were taken forward and further assessed for clinical relevance using OncomiR and previously published literature. One hundred and thirty significant survival associations for 46 microRNAs across fourteen groups of cancers were identified. Finally, a total of 23 putative repurposed drugs targeting multiple components of the PDCD1/CD274 network were identified, which may represent immunotherapeutic adjuvants. Taken together, these results shed light on the varying PDCD1/CD274 networks between individual cancers and signpost a need for more cancer-specific investigations and treatments.

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Section: Discussionsupporting

confidence: 85%

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study

Kannan

O’Connor

Bakker

2021

IJMS

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“…The exact function or contribution of exo‐miRNA in carcinogenesis can be complex given the large number of mRNA targets for each miRNA. To this point, miR‐125a‐5p, a known tumor suppressor miRNA for multiple cancer types, 33 , 34 , 35 , 36 , 37 including HNSCC, 38 , 39 has more than 900 experimentally confirmed targets (TarBase v7.0), which include numerous cancer‐associated pathways. To our knowledge, at the time of submission, miR‐3168 had no experimentally confirmed targets.…”

Section: Discussionmentioning

confidence: 99%

Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection

et al. 2022

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Background: The objective was to assess secretion of small extracellular vesicular microRNA (exo-miRNA) in head and neck squamous cell carcinoma (HNSCC) according to human papillomavirus (HPV) status, and determine the translational potential as a liquid biopsy for early detection. Methods: This study employed a combination of cell culture and case-control study design using archival pretreatment serum. Small extracellular vesicles (sEV) were isolated from conditioned culture media and human serum samples via differential ultracentrifugation. miRNA-sequencing was performed on each sEV isolate. Results: There were clear exo-miRNA profiles that distinguished HNSCC cell lines from nonpathologic oral epithelial control cells. While there was some overlap among profiles across all samples, there were apparent differences in exo-miRNA profiles according to HPV-status. Importantly, differential exo-miRNA profiles were also apparent in serum from early-stage HNSCC cases relative to cancer-free controls.

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“…In mouse in vivo and in vitro models of thyroiditis, an increased miR-125a expression reduces autophagy and cell proliferation and increases the apoptotic rate and the expression of proinflammatory factors tumor necrosis factor-α, IL-1β, IL-6, and IL-18 via downregulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR)signaling pathway [32]. Low levels of miR-125a-5p are found in different types of tumors [33]. Levels of miR-125a-5p are also found to be decreased in the hippocampus of rats with pentylenetetrazol (PTZ)-induced epilepsy, whereas miR-125a-5p overexpression can attenuate seizures and decrease inflammatory factors in these rats [34].…”

Section: Discussionmentioning

confidence: 99%

Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome

Putkonen

Laiho

Ethell³

et al. 2020

Cells

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A triplet repeat expansion leading to transcriptional silencing of the FMR1 gene results in fragile X syndrome (FXS), which is a common cause of inherited intellectual disability and autism. Phenotypic variation requires personalized treatment approaches and hampers clinical trials in FXS. We searched for microRNA (miRNA) biomarkers for FXS using deep sequencing of urine and identified 28 differentially regulated miRNAs when 219 reliably identified miRNAs were compared in dizygotic twin boys who shared the same environment, but one had an FXS full mutation, and the other carried a premutation allele. The largest increase was found in miR-125a in the FXS sample, and the miR-125a levels were increased in two independent sets of urine samples from a total of 19 FXS children. Urine miR-125a levels appeared to increase with age in control subjects, but varied widely in FXS subjects. Should the results be generalized, it could suggest that two FXS subgroups existed. Predicted gene targets of the differentially regulated miRNAs are involved in molecular pathways that regulate developmental processes, homeostasis, and neuronal function. Regulation of miR-125a has been associated with type I metabotropic glutamate receptor signaling (mGluR), which has been explored as a treatment target for FXS, reinforcing the possibility that urine miR-125a may provide a novel biomarker for FXS.

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Prognostic and clinicopathologic significance of MicroRNA-125a-5p in cancers

Cited by 6 publications

References 30 publications

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study

Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study

Small extravesicular microRNA in head and neck squamous cell carcinoma and its potential as a liquid biopsy for early detection

Urine microRNA Profiling Displays miR-125a Dysregulation in Children with Fragile X Syndrome

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