The Role of CTNNA1 in Malignancies: An Updated Review

Huang, Jinhua; Xu, Yuting; Li, Chunhua; Lv, Xinyue; Han, Xintong; Chen, Xiaochun; Chen, Yu; Zhang, Yu

doi:10.7150/jca.79236

Cited by 4 publications

(1 citation statement)

References 93 publications

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“…α-catenin (CTNNA)1, which is widely expressed in normal human tissues and in many malignancies, inhibits adhesion, invasion, and induces apoptosis of tumor cells by promoting or collaborating with E-cadherin. The expression of CTNNA1 is downregulated in different types of tumors, and it is often associated with reduced expression of other proteins of E-cadherin–catenin cell adhesion complex [ 40 ]. Among the top regulated pathways in our DIANA tool mirPath v.3 analysis is Adherens junction, where CTNNA1 and CTNNA2 are key factors.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings

et al. 2023

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Actinic keratosis (AK) is a carcinoma in situ precursor of cutaneous squamous cell carcinoma (cSCC), the second most common cancer affecting the Caucasian population. AK is frequently present in the sun-exposed skin of the elderly population, UV radiation being the main cause of this cancer, and other risk factors contributing to AK incidence. The dysregulation of microRNAs (miRNAs) observed in different cancers leads to an improper expression of miRNA targets involved in several cellular pathways. The TaqMan Array Human MicroRNA Card assay for miRNA expression profiling was performed in pooled AK compared to healthy skin scraping samples from the same patients. Forty-three miRNAs were modulated in the AK samples. The expression of miR-19b (p < 0.05), -31, -34a (p < 0.001), -126, -146a (p < 0.01), -193b, and -222 (p < 0.05) was validated by RT-qPCR. The MirPath tool was used for MiRNA target prediction and enriched pathways. The top DIANA-mirPath pathways regulated by the targets of the 43 miRNAs are TGF-beta signaling, Proteoglycans in cancer, Pathways in cancer, and Adherens junction (7.30 × 10−10 < p < 1.84 × 10−8). Selected genes regulating the KEGG pathways, i.e., TP53, MDM2, CDKN1A, CDK6, and CCND1, were analyzed. MiRNAs modulated in AK regulate different pathways involved in tumorigenesis, indicating miRNA regulation as a critical step in keratinocyte cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings

et al. 2023

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Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men

Hayes,

Gong,

Jiang

et al. 2024

Preprint

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Prostate cancer (PCa) is highly heritable, with men of African ancestry at greatest risk and associated lethality. Lack of representation in genomic data means germline testing guidelines exclude for African men. Established that structural variations (SVs) are major contributors to human disease and prostate tumourigenesis, their role is under-appreciated in familial and therapeutic testing. Utilising a clinico-methodologically matched African (n = 113) versus European (n = 57) deep-sequenced PCa resource, we interrogated 42,966 high-quality germline SVs using a best-fit pathogenicity prediction workflow. We identified 15 potentially pathogenic SVs representing 12.4% African and 7.0% European patients, of which 72% and 86% met germline testing standard-of-care recommendations, respectively. Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African associated disparity.

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Reduction of Phosphorylated Tau in Alzheimer’s Disease Induced Pluripotent Stem Cell-Derived Neuro-Spheroids by Rho-Associated Coiled-Coil Kinase Inhibitor Fasudil

Giunti,

Collu,

Daley

et al. 2023

JAD

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Background: Alzheimer’s disease (AD) is the most predominant form of dementia. Rho-associated coiled coil kinase (ROCK) inhibitor, fasudil, is one of the candidate drugs against the AD progression. Objective: We aimed to investigate possible changes of AD associated markers in three-dimensional neuro-spheroids (3D neuro-spheroids) generated from induced pluripotent stem cells derived from AD patients or healthy control subjects (HC) and to determine the impact of pharmacological intervention with the ROCK inhibitor fasudil. Methods: We treated 3D neuro-spheroids with fasudil and tested the possible effect on AD markers by ELISA, transcriptomic and proteomic analyses. Results: Transcriptomic analysis revealed a reduction in the expression of AKT serine/threonine-protein kinase 1 (AKT1) in AD neuro-spheroids, compared to HC. This decrease was reverted in the presence of fasudil. Proteomic analysis showed up- and down-regulation of proteins related to AKT pathway in fasudil-treated neuro-spheroids. We found an evident increase of phosphorylated tau at four different residues (pTau181, 202, 231, and 396) in AD compared to HC-derived neuro-spheroids. This was accompanied by a decrease of secreted clusterin (clu) and an increase of intracellular clu levels in AD patient-derived neuro-spheroids. Increases of phosphorylated tau in AD patient-derived neuro-spheroids were suppressed in the presence of fasudil. Conclusions: Fasudil modulates clu protein levels and enhances AKT1 that results in the suppression of AD associated tau phosphorylation.

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The Role of CTNNA1 in Malignancies: An Updated Review

Cited by 4 publications

References 93 publications

MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings

MicroRNAs Differentially Expressed in Actinic Keratosis and Healthy Skin Scrapings

Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men

Reduction of Phosphorylated Tau in Alzheimer’s Disease Induced Pluripotent Stem Cell-Derived Neuro-Spheroids by Rho-Associated Coiled-Coil Kinase Inhibitor Fasudil

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