CNOT3 and Associated Diseases
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Overview of CNOT3
CCR4-NOT transcription complex subunit 3 (CNOT3, also known as CCR4-associated factor 3 or leukocyte receptor cluster member 2) is a protein encoded by CNOT3 in humans. CNOT3 is a member of the CCR4-NOT complex, one of the key cellular mRNA deadenylases, and is involved in several cellular functions such as transcriptional regulation. The CCR4-NOT complex and transcriptional control are associated with CNOT3, which can suppress transcription through bulk mRNA degradation, miRNA-mediated repression, and translational repression. Histone deacetylases are involved during the repressive function.
CNOT3 in Disease
CNOT3-associated diseases contain lung cancer, heart diseases like myocardium damage, and intellectual developmental disorder with speech delay, autism, and dysmorphic facies.
- Lung cancer
CNOT3 participates in lung cancer (LC) progression by RIPK3 inhibition. LC is still the most frequently diagnosed malignancy, and lung cancer patients always have poor clinical outcomes due to chemotherapeutic resistance. CNOT3 is involved in cancer development and chemotherapeutic resistance. Upregulated expression of CNOT3 is observed in lung cancer tissues and predicts a poor prognosis in LC patients. In chemo-resistant LC cells, higher expression of CNOT3 and low RIPK3 expression is observed. Knockdown of CNOT3 can sensitize the chemo-resistant LC cells and induce apoptosis by the elevated RIPK3 expression and RIPK3-triggered caspase 8 activations.
Fig.1 Elevated CNOT3 expression is observed in LC tissues than in normal tissues. (Jing, 2019)
- Myocardium damage
CNOT3-related mRNA degradation plays an important role in cardiomyocyte growth to compensate for disease-damaged myocardium. Myocardium damage can influence normal myocardium function and blood supply and have the potential of myocardial infarction, which can further cause permanent heart damage and death. CNOT3 functions as a regulator of cardiomyocyte proliferation during cardiac differentiation from human ESCs. High expression of CNOT3 occurs in cardiomyocytes with higher proliferation potential, and depletion of CNOT3 leads to significantly reduced proliferative capacity. Overexpression of CNOT3 can enhance proliferation in both cultured cardiomyocytes of humans and infarcted mouse hearts by degrading anti-proliferation gene transcripts. Taken together, CNOT3 controls cardiac cell fates and promotes cardiomyocyte growth to partly rescue disease-damaged myocardium.
With the aid of cutting-edge technology and years of experience, Creative Biolabs has built several reliable evaluation tools for the development of gene therapy. Our expertise in all gene therapy procedures will undoubtedly hasten the development of your idea. Please feel free to contact us for more details about your CNOT3 project.
References
- Jing, L.; et al. CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression. Apoptosis. 2019, 24: 673–685.
- Zhou, B.; et al. CNOT3 enhances human embryonic cardiomyocyte proliferation by promoting cell cycle inhibitor mRNA degradation. Sci Rep. 2017, 7: 1500.
