Article Abstract

Cyclin-dependent kinase 7 (CDK7) expression in human hepatocellular carcinoma: association with HCC progression, prognosis and cell proliferative capacity

Authors: Zheran Liu, Dajiao Liu, Rongrong Zhong, Qiuyun Su, Tiancheng Zhao, Fen Fu, Jinsheng Liu, Derong Xu, Changqing Zeng

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and contributes to a high cancer mortality globally. The multistep progression of HCC is highly related to the activation of oncogenes and the deactivation of cancer suppressor genes. The cyclin-dependent kinase 7 (CDK7) gene is responsible for maintaining a normal cell cycle, acting as a gatekeeper, and plays an important part in RNA transcription. Although previous studies demonstrate that CDK7 is highly expressed in multiple cancers and is associated with the progression and prognosis of these cancers, the potential role of CDK7 in HCC still needs to be explored.
Methods: Data consisting of CDK7 expression levels, patient phenotypes and their matched survival were acquired from The Cancer Genome Atlas (TCGA) database. The associations of the CDK7 expression level with clinicopathological factors and cell proliferation were analyzed. The HCC transcriptome data in the GEO database were inquired and analyzed using GEO2R. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when CDK7 expression was inhibited by either shCDK7 or THZ1.
Results: Based on the transcriptome and survival data in the TCGA database, the CDK7 expression level was inversely proportional to the overall survival of the HCC patients (pooled HR =1.51, 95% CI =1.06–2.15). For further investigation, the clinical features of HCC were integrated with the expression level of CDK7. A high expression of CDK7 was proportional to the survival time of the HCC patients (P=2.38×10−3), the neoplasm histologic grade (P<1×10−4) and cell proliferation (P<1×10−3). Moreover, CDK7 expression in the liver tumor was higher than that in non-tumor tissues (t-test =6.04, P=2.27×10−8). For HCC patients, CDK7 expression was higher in the tumor tissues than in the para-carcinoma tissues, based on five GEO datasets (Z score =−6.20, P=5.64×10−10). In the SMMC-7721 and Huh7 cell lines, CDK7 shRNA-transfected cells showed significantly lower capabilities of cell growth and proliferation than those of the shRNA control group after 48 hours of cell culture. Furthermore, the cell proliferation capacity was also inhibited when the SMMC-7721 cells (P=6.47×10−2) or Huh7 cells (P=2.52×10−2) were exposed to THZ1.
Conclusions: The CDK7 expression level in HCC is associated with HCC progression, prognosis and the cell proliferation capacity. CDK7 may act as a potential target for HCC, and THZ1 might be a potent medicine for HCC treatment.