Abstract
BackgroundDNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs), whose function in hepatocellular carcinoma has not been investigated.MethodsIn the present study, both the data collected from the Cancer Genome Atlas (TCGA) and our group’s results showed higher POLQ expression in HCC tissues than the para-cancerous tissues, which was associated with higher malignancy and poor prognosis. POLQ knockdown HCC cell model (shPOLQ) was constructed along with the corresponding negative control (shCtrl) through lentivirus infection for loss-of-function study.ResultsWe found that, upon knockdown of POLQ, the proliferation and migration of HCC cells decreased and apoptosis percentage increased. Moreover, the percentage of cells in G2 phase significantly increased in shPOLQ group compared with shCtrl group. Xenografts in mice grafted with shPOLQ cells grew much slower than that transplanted with shCtrl cells, and expressed lower Ki67 level. Furthermore, an apoptosis-related signaling array was used to explore the involvement of downstream signaling pathways, suggesting the enhanced phosphorylation of HSP27 and JNK, and the de-activation of mTOR, PRAS40, ERK1/2 and STAT3 pathways.ConclusionsCollectively, our study revealed that POLQ may participate in the development of HCC, depletion of which may be a promising treatment strategy for HCC.
Highlights
In the past decades, malignant tumors have become one of the leading causes of human death worldwide
POLQ is upregulated in hepatocellular carcinoma (HCC) and associated with HCC development First of all, the expression of POLQ in 50 normal tissues and 374 tumor tissues was collected from LIHC dataset of the Cancer Genome Atlas (TCGA) database
The results indicated the significantly upregulation of POLQ in HCC (Fig. 1A), which probably predicts the poor prognosis of HCC patients (Fig. 1B)
Summary
Malignant tumors have become one of the leading causes of human death worldwide. According to the latest statistics, among all malignant tumors, the incidence and mortality of liver cancer ranks sixth and fourth, respectively [1, 2]. Among all types of primary liver cancer, Pan et al Cancer Cell Int (2021) 21:482 hepatocellular carcinoma (HCC) accounts for more than 80%, which is the most important histological type [3]. The treatment of HCC is a combination of surgical resection and chemotherapy [4]. Surgical resection has a good curative effect on early HCC, due to the small diameter of tumor and the lack of typical clinical symptoms and signs, the patient’s tumor frequently has progressed to the advanced stage at the time of diagnosis. DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs), whose function in hepatocellular carcinoma has not been investigated
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