scholarly journals Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manveen K. Gupta ◽  
Anita Sahu ◽  
Yu Sun ◽  
Maradumane L. Mohan ◽  
Avinash Kumar ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Significant Loss ◽  
Transverse Aortic Constriction ◽  
Cardiac Physiology ◽  
Aortic Constriction ◽  
Hypertrophic Response ◽  
Erbb2 Expression ◽  
Physiological Cardiac Hypertrophy ◽  
Epidermal Growth

AbstractAlthough microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to determine its role in cardiac physiology and pathology. Echocardiography on the miRNA-7 Tg mice showed cardiac dilation instead of age-associated physiological cardiac hypertrophy observed in non-Tg control mice. Subjecting miRNA-7 Tg mice to transverse aortic constriction (TAC) resulted in cardiac dilation associated with increased fibrosis bypassing the adaptive cardiac hypertrophic response to TAC. miRNA-7 expression in cardiomyocytes resulted in significant loss of ERBB2 expression with no changes in ERBB1 (EGFR). Cardiac proteomics in the miRNA-7 Tg mice showed significant reduction in mitochondrial membrane structural proteins compared to NTg reflecting role of miRNA-7 beyond the regulation of EGFR/ERRB in mediating cardiac dilation. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized rounded mitochondria that was associated with mitochondrial dysfunction. These findings show that expression of miRNA-7 in the cardiomyocytes results in cardiac dilation instead of adaptive hypertrophic response during aging or to TAC providing insights on yet to be understood role of miRNA-7 in cardiac function.

scholarly journals Cardiac overexpression of microRNA-7 is associated with adverse cardiac remodeling

2020 ◽  
Author(s):  
Manveen K Gupta ◽  
Anita Sahu ◽  
Xi Wang ◽  
Elizabeth E. Martelli ◽  
Kate Stenson ◽  
...  
Keyword(s):  
Membrane Integrity ◽  
Growth Factor Receptor ◽  
Significant Loss ◽  
Cardiac Cells ◽  
Mitochondrial Morphology ◽  
Proteomics Data ◽  
Hypertrophic Response ◽  
Adverse Remodeling ◽  
Epidermal Growth ◽  
Similar Survival

AbstractRole of microRNA-7 (miRNA-7) in targeting Epidermal growth factor receptor (EGFR/ERBB) family is known in dividing cancer cells while less is known about its role in terminally differentiated cardiac cells. We generated transgenic (Tg) mice with cardiomyocyte-specific overexpression of miRNA-7 to determine its role in regulating cardiac function. Despite similar survival, expression of miRNA-7 results in cardiac dilation as measured by echocardiography, instead of age-based cardiac hypertrophy observed in littermate controls. In contrast to the classical adaptive hypertrophy in response to TAC, miRNA-7 Tg mice directly undergo cardiac dilation post-TAC that is associated with increased fibrosis. Interestingly, significant loss in ERBB2 expression was observed in cardiomyocytes with no changes in ERBB1 (EGFR). Gene ontology and cellular component analysis using the cardiac proteomics data showed significant reduction in mitochondrial membrane integrity reflecting the differential enrichment/loss of proteins in miRNA-7 Tg mice compared to littermate controls. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized and rounded mitochondrial morphology indicating mitochondrial dysfunction. These findings show that expression of miRNA-7 uniquely results in cardiac dilation instead of adaptive hypertrophic response to cardiac stress providing insights on adverse remodeling in physiology and pathology.

Abstract 120: Epidermal Growth Factor Receptor (EGFR) Family Dimeric Partners Switch During Pathological Stress in microRNA-7 Transgenic Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Manveen Gupta ◽  
Xi Wang ◽  
Elizabeth Martelli ◽  
Sathyamangla V Naga Prasad
Keyword(s):  
Cardiac Dysfunction ◽  
Biochemical Analysis ◽  
Growth Factor Receptor ◽  
Aortic Constriction ◽  
Human Heart Failure ◽  
Hypertrophic Response ◽  
Downstream Signaling ◽  
Age Dependent ◽  
Epidermal Growth ◽  
Egfr Family

miRNA-7 is known to target epidermal growth factors receptor 1(EGFR1) in cancer cells. EGFR family members (EGFR 1, 2, 3 and 4) are known to form homo- and/or hetero-dimers to mediate downstream signals . Our previous study in human heart failure (Naga Prasad etal., JBC, 2009) showed that EGFR2 (ERBB2) was targeted by miRNA-7. Based on this study, we developed transgenic (Tg) mice with cardiomyocyte-specific overexpression of miRNA-7. miRNA-7 Tg mice have age dependent deterioration in cardiac dysfunction and is associated with cardiac dilation as measured by echocardiography (3 months - 60% FS, 6 month -52% FS &12 months - 24%FS) and yet, they survive well for more than a year. To investigate whether pathological stress would accelerate the deterioration in cardiac function, miRNA-7 Tg mice were subjected to transverse aortic constriction (TAC) for two weeks. In contrast to the wild type littermates which undergo hypertrophic response following TAC, miRNA-7 Tg mice have accelerated cardiac dysfunction and dilation within two weeks. Biochemical analysis interestingly showed differential switching of dimeric EGFR partners in hearts of the miRNA-7 Tg mice compared to their sham controls. Our presentation will discuss the differential downstream signaling induced by changing of EGFR dimeric partners induced by pathological stress like TAC in the wildtype and miRNA-7 Tg mice.

scholarly journals Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

Oncogene ◽  
2006 ◽  
Vol 26 (23) ◽  
pp. 3431-3439 ◽  
Author(s):  
F Y Feng ◽  
S Varambally ◽  
S A Tomlins ◽  
P Y Chun ◽  
C A Lopez ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals The Role of Canonical Wnt Signaling in Regulating Radioresistance

2018 ◽  
Vol 48 (2) ◽  
pp. 419-432 ◽  
Author(s):  
Yuanyuan Zhao ◽  
Leilei Tao ◽  
Jun Yi ◽  
Haizhu Song ◽  
Longbang Chen
Keyword(s):  
Wnt Signaling ◽  
Cancer Progression ◽  
Wnt Signaling Pathway ◽  
Growth Factor Receptor ◽  
Cancer Resistance ◽  
Canonical Wnt Signaling ◽  
Damage Repair ◽  
Epidermal Growth ◽  
Canonical Wnt

Radioresistance is a major obstacle in radiotherapy for cancer, and strategies are needed to overcome this problem. Currently, radiotherapy combined with targeted therapy such as inhibitors of phosphoinosotide 3-kinase/Akt and epidermal growth factor receptor signaling have become the focus of studies on radiosensitization. Apart from these two signaling pathways, which promote radioresistance, deregulation of Wnt signaling is also associated with the radioresistance of multiple cancers. Wnts, as important messengers in the tumor microenvironment, are involved in cancer progression mainly via canonical Wnt signaling. Their role in promoting DNA damage repair and inhibiting apoptosis facilitates cancer resistance to radiation. Thus, it seems reasonable to target Wnt signaling as a method for overcoming radioresistance. Many small-molecule inhibitors that target the Wnt signaling pathway have been identified and shown to promote radiosensitization. Therefore, a Wnt signaling inhibitor may help to overcome radioresistance in cancer therapy.

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