Knockdown of POLQ interferes the development and progression of hepatocellular carcinoma through regulating cell proliferation, apoptosis and migration

Qi Pan; Lu Wang; Yu Liu; Min Li; Yao Zhang; Wei Peng; Tan Deng; Mei-Ling Peng; Jin-Qiong Jiang; Jiao Tang; Jingjing Wang; Hua-Xin Duan; Sha-Sha Fan

doi:10.1186/s12935-021-02178-2

Knockdown of POLQ interferes the development and progression of hepatocellular carcinoma through regulating cell proliferation, apoptosis and migration

Cancer Cell Int. 2021 Sep 13;21(1):482. doi: 10.1186/s12935-021-02178-2.

Authors

Qi Pan^#¹, Lu Wang^#¹, Yu Liu^#², Min Li³, Yao Zhang³, Wei Peng³, Tan Deng³, Mei-Ling Peng³, Jin-Qiong Jiang³, Jiao Tang³, Jingjing Wang⁴, Hua-Xin Duan⁵, Sha-Sha Fan⁶

Affiliations

¹ Department of Hepatic Surgery, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
² Department of Pathology, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, Changsha, 410000, Hunan, China.
³ Oncology Department, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, 410000, Hunan, China.
⁴ Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, 410000, Hunan, China.
⁵ Oncology Department, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, 410000, Hunan, China. duanhuaxin@hunnu.edu.cn.
⁶ Oncology Department, The First Affiliated Hospital of Hunan Normal University, Hunan Provincial People's Hospital, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha, 410000, Hunan, China. shashafan0225@hunnu.edu.cn.

^# Contributed equally.

Abstract

Background: 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.

Methods: In 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.

Results: We 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.

Conclusions: Collectively, our study revealed that POLQ may participate in the development of HCC, depletion of which may be a promising treatment strategy for HCC.

Keywords: Cell apoptosis; Cell migration; Cell proliferation; Hepatocellular carcinoma; POLQ.

Abstract

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