Cyclin ‐dependent kinase 9 promotes cervical cancer development via AKT2/p53 pathway

AbstractAberrant activation of cyclin ‐dependent kinase 9 (CDK9) is widespread in human cancers. However, the underlying mechanisms of CDK9 activation and the therapeutic potential of CDK9 inhibition in cervical cancer remain largely unknown. Here, we report that CDK9 is gradually upregulated during cervical lesion progression and reg ulated by HPV16 E6. CDK9 levels are highly correlated with FIGO stage, pathological grade, deep‐stromal invasion, tumor size, and lymph nodes metastasis. Knockdown of CDK9 by specific siRNA inhibits cervical cancer cell proliferation in vitro, as well as tumorigenesis in vivo. CDK9 inhibition caus es a significant decreased AKT2 and increased p53 protein expression revealing novel CDK9‐regulatory mechanisms. Overexpression of AKT2 rescued the suppressive effects caused by CDK9 knockdown, suggesting that AKT2 induction is essential for CDK9‐induced transformation. Moreover, CDK9 expression was positively correlated with AKT2 and negatively correlated with p53 in cervical cancer tissues with HPV16 infection. Our findings demonstrate for the first time that CDK9 acts as a proto‐oncogene in cervical cancer, modulating cell proliferation and apoptosis through AKT2/p53 pathway. Therefor e, our data provide novel mechanistic insights into the role of CDK9 in cervical cancer development. © 2018 IUBMB Life, 2018
Source: IUBMB Life - Category: Research Authors: Tags: Research Communication Source Type: research

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Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research
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Source: Indian Journal of Surgical Oncology - Category: Cancer & Oncology Source Type: research
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Source: Guardian Unlimited Science - Category: Science Authors: Tags: NHS Health Cervical cancer Health policy Public services policy Science Society Politics UK news Source Type: news
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Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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