J Cancer 2020; 11(15):4308-4315. doi:10.7150/jca.42849
CDK12 promotes papillary thyroid cancer progression through regulating the c-myc/β-catenin pathway
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
Bai N, Xia F, Wang W, Lei Y, Bo J, Li X. CDK12 promotes papillary thyroid cancer progression through regulating the c-myc/β-catenin pathway. J Cancer 2020; 11(15):4308-4315. doi:10.7150/jca.42849. Available from http://www.jcancer.org/v11p4308.htm
Background: CDK12 is a potential therapeutic target in papillary thyroid cancer that regulates the c-myc/β-catenin pathway.
Objective: We aimed to explore the specific mechanism of CDK12 in papillary thyroid cancer and provide a new target of cancer therapy.
Methods: 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 in vivo 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.
Results: Upregulated CDK12 expression in papillary thyroid cancer promoted papillary thyroid cancer carcinogenesis in vivo, and in vitro CDK12 strengthened papillary thyroid cancer (PTC) cell migration and tumor metastasis. CDK12 promoted tumor progression by regulating c-myc/β-catenin pathway activation.
Conclusions: 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.
Keywords: CDK12, papillary thyroid cancer, c-myc, β-catenin, cancer progression