Bai Ning, Xia Fada, Wang Wenlong, Lei Yao, Bo Jiang, Li Xinying
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
J Cancer. 2020 Apr 27;11(15):4308-4315. doi: 10.7150/jca.42849. eCollection 2020.
: CDK12 is a potential therapeutic target in papillary thyroid cancer that regulates the c-myc/β-catenin pathway. : We aimed to explore the specific mechanism of CDK12 in papillary thyroid cancer and provide a new target of cancer therapy. : RT-qPCR was used to determine the CDK12 mRNA expression level. An IHC assay was performed to detect the tissue expression of CDK12. Then, we downregulated CDK12 expression in the thyroid cancer cell lines TPC-1-shCDK12 and KAT-5-shCDK12. CCK8 assays, colony formation assays, and animal xenograft models were used to evaluate the effect of CDK12 on tumorigenesis. Transwell assays and metastasis models were used to observe whether CDK12 can promote cancer metastasis. Western blotting further confirmed the mechanism of CDK12 in papillary thyroid cancer through the c-myc/β-catenin pathway. : Upregulated CDK12 expression in papillary thyroid cancer promoted papillary thyroid cancer carcinogenesis , and CDK12 strengthened papillary thyroid cancer (PTC) cell migration and tumor metastasis. CDK12 promoted tumor progression by regulating c-myc/β-catenin pathway activation. : CDK12 affects the c-myc/β-catenin pathway to stimulate papillary thyroid cancer proliferation and metastasis. Inhibiting CDK12 might be a new method in papillary thyroid cancer therapy.
CDK12是甲状腺乳头状癌中一个潜在的治疗靶点,它调控c-myc/β-连环蛋白通路。我们旨在探究CDK12在甲状腺乳头状癌中的具体机制,并提供一个新的癌症治疗靶点。采用RT-qPCR测定CDK12 mRNA表达水平。进行免疫组化分析以检测CDK12的组织表达。然后,我们在甲状腺癌细胞系TPC-1-shCDK12和KAT-5-shCDK12中下调CDK12表达。使用CCK8分析、集落形成分析和动物异种移植模型来评估CDK12对肿瘤发生的影响。采用Transwell分析和转移模型来观察CDK12是否能促进癌症转移。蛋白质免疫印迹法通过c-myc/β-连环蛋白通路进一步证实了CDK12在甲状腺乳头状癌中的作用机制。甲状腺乳头状癌中CDK12表达上调促进了甲状腺乳头状癌的发生,并且CDK12增强了甲状腺乳头状癌(PTC)细胞的迁移和肿瘤转移。CDK12通过调节c-myc/β-连环蛋白通路的激活促进肿瘤进展。CDK12影响c-myc/β-连环蛋白通路以刺激甲状腺乳头状癌的增殖和转移。抑制CDK12可能是甲状腺乳头状癌治疗的一种新方法。