NEIL3 contributes toward the carcinogenesis of liver cancer and regulates PI3K/Akt/mTOR signaling

Abstract

Liver cancer is one of the top three fatal types of cancer and it causes several thousands of mortalities each year. The main treatment is surgical resection which shows little benefit for patients with recurrence or metastasis. NEIL3 promotes progression and predicts survival in cancer. However, its role in liver cancer remains unclear. Based on data in the TCGA database, NEIL3 exhibited much higher expression in liver cancer tissues and was clinically correlated with tumor grade in patients with liver cancer. Furthermore, high NEIL3 expression caused shorter survival times. In liver cancer cell lines, NEIL3 showed abundant expression. When NEIL3 was knocked down in HepG2 and Huh-7 cells, cell abilities including proliferation, growth, migration and invasion, exhibited deficiency to different extents. Cell cycle transition was blocked at the G2 phase and the cell apoptotic rate increased notably. In addition, the phosphorylation levels of Akt, PI3K and mTOR were increased following NEIL3-overexpression but decreased following NEIL3-knockdown. In conclusion, NEIL3 contributes toward development and/or progression in liver cancer and regulates PI3K/Akt/mTOR signaling.

NEIL3 Mediates Lung Cancer Progression and Modulates PI3K/AKT/mTOR Signaling: A Potential Therapeutic Target

“…In patients with high NEIL3 expressions, the PI3K/AKT/mTOR pathway, G2/M checkpoints, and E2F targets were aberrantly activated ( Figure 6(a) ). A previous study reported that NEIL3 can affect the activities of the PI3K/AKT/mTOR signaling pathway [ 15 ]. Therefore, we evaluated whether the cancer-promoting effects of NEIL3 in NSCLC are mediated by PI3K/AKT/mTOR signaling.…”

“…Given the biological effects of NEIL3 on genomic stability, it may have oncogenic effects. The underlying mechanisms of NEIL3 in cancer have attracted extensive attention, making it an attractive therapeutic target for specific cancers [ 15 ]. Zhao et al found that NEIL3 prevents senescence in liver cancer by repairing oxidative lesions at telomeres during mitosis, contributing to poor prognostic outcomes [ 21 ].…”

“…In addition, NEIL3 is involved in human malignancy. Wang et al reported that NEIL3 contributes towards liver cancer carcinogenesis by regulating the PI3K/Akt/mTOR signaling [ 15 ]. Moreover, Tran et al found that NEIL3 might be associated with genomic mutations and chromosomal variations [ 16 ].…”

DNA Damage Response Gene-Based Subtypes Associated With Clinical Outcomes in Early-Stage Lung Adenocarcinoma

“…Many studies have reported that they are significantly correlated with prognosis in different cancer types, such as colorectal cancer, pancreatic cancer, gastric cancer, and so on ( Luo et al, 2018 ; Zhang et al, 2019 ; Li et al, 2021 ). NEIL3 , PCNA , RFC3 , and POLD2 play important roles in the BER pathway which are recruited to DNA lesions and cleave and repair the damaged bases cooperatively ( Robertson et al, 2009 ; Hurst et al, 2021 ; Wang et al, 2021 ). Zhao et al found that NEIL3 activated cell cycle progression, leading to poor prognosis ( Zhao et al, 2021 ).…”

Identification of DNA Damage Repair-Associated Prognostic Biomarkers for Prostate Cancer Using Transcriptomic Data Analysis

“…NEIL3 can secure mitotic chromosome segregation by repairing telomere damage [ 60 ], although deficiency of NEIL3 was reported to enhance resistance to chemotherapy in PC [ 61 ]. Alterations of NEIL3 are also associated with somatic mutation loads, carcinogenesis, and poor survival in many human cancers [ 62 , 63 , 64 ]. EME2 can promote restart of replication fork and the genetic change of EME2 and is therefore associated with DDR in malignancies [ 65 , 66 ].…”