The Biological Function of POLA2 in Hepatocellular Carcinoma

Title:The Biological Function of POLA2 in Hepatocellular Carcinoma

Volume: 27 Issue: 12

Author(s): Zhen Yang, Xingyuan Shen, Zhihuai Wang, Renzhi Li, Wenqiang Hou, Zengyuan Liu, Yuan Gao, Chunfu Zhu*Xihu Qin*

Affiliation:

• Dalian Medical University, Dalian, Liaoning, 116000, China
• Department of General Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213000, China

• Dalian Medical University, Dalian, Liaoning, 116000, China
• Department of General Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213000, China

Keywords: POLA2, hepatocellular carcinoma, proliferation, PI3K/AKT/mTOR pathway, immune infiltration, immune cell types' genetic markers.

Abstract:

Introduction: The role and prognostic value of POLA2 in liver cancer were comprehensively analyzed through TCGA, GEO, and ICGC databases, and the role of POLA2 in liver cancer cells and the regulatory mechanism involved were further verified through cell experiments. Hepatocellular carcinoma (HCC) is the most prevalent malignancy with high morbidity and mortality. Consequently, it is critical to identify robust and reliable predictive biomarkers and therapeutic targets for HCC patients. POLA2 is involved in the regulation of various tumors, but the specific role of POLA2 in HCC has not been reported. The regulatory role and prognostic value of POLA2 in HCC were determined by bioinformatics techniques and cell experiments.

Methods: The specific role and prognostic value of POLA2 in HCC were comprehensively analyzed by combining the expression data of POLA2 in TCGA, GEO, and ICGC databases and clinical data. In clinical samples, the expression of POLA2 in liver cancer was verified by QPCR. Further, the regulatory role of POLA2 in HCC was explored through cell experiments such as CCK-8, clonal formation experiment, EDU cell proliferation experiment, and flow cytometry. In terms of mechanism exploration, western blot was used to verify the specific regulatory mechanism that POLA2 participated in. Finally, the relationship between POLA2 and immune invasion of HCC was analyzed by using the TIMER database.

Results: A POLA2 expression and prognosis analysis of HCC patients was conducted using the TCGA, GEO, and ICGC databases. We hypothesized that POLA2 might be one of the key factors contributing to the HCC progression. According to a combined analysis of TCGA, ICGC, and GEO databases, POLA2 was highly expressed in HCC. This was further confirmed in clinical samples using the qPCR. POLA2 knockdown was also performed in vitro on HCC cell lines to study the changes in their biological behavior. We confirmed that POLA2 was associated with HCC proliferation by CCK-8, Colony Formation, and EDU assay. We verified the POLA2's involvement in cell cycle regulation using flow techniques. The relationship between POLA2 and PI3K/AKT/mTOR pathway was explored using Western Blotting experiments regarding its mechanism. Further analysis revealed that the POLA2 expression was significantly associated with HCC immune infiltration.

Conclusion: Our study demonstrated POLA2's importance in HCC development and progression and its potential role as a biomarker for disease progression on multiple levels. POLA2 has an important role in regulating the cell cycle and cell proliferation. By interfering with the cell cycle and proliferation, HCC cell growth is inhibited. Furthermore, POLA2 expression was significantly associated with immune infiltration. POLA2 may play a role in HCC immunotherapy based on its correlation with several immune cell types' genetic markers. The findings of this study are expected to lead to new anticancer strategies for HCC.

Cite this article as:

Yang Zhen, Shen Xingyuan, Wang Zhihuai, Li Renzhi, Hou Wenqiang, Liu Zengyuan, Gao Yuan, Zhu Chunfu*, Qin Xihu*, The Biological Function of POLA2 in Hepatocellular Carcinoma, Combinatorial Chemistry & High Throughput Screening 2024; 27 (12) . https://dx.doi.org/10.2174/0113862073254083231002052550