HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer

Xubin Liu,Meng Xia,Hanyu Ma,Lihong Bai,Xufang Pi,Shangwu Chen,Li Yu,Lingyan Fei,Mengjie Jiang

doi:10.1186/s13027-020-0272-3

Abstract

Cervical cancer is the fourth most common malignant tumor in women worldwide. The persistent infection of high-risk Human Papillomavirus (hrHPV) is considered to be the primary cause of this disease. As an innate immune receptor, the nucleotide-binding oligomerization domain protein-1 (NOD1) recognizes the pathogen-associated molecular pattern (PAMP), subsequently initiating immune responses. NOD1 is also involved in the apoptotic signaling pathway and mutates in many cancer cells. In the study, we revealed that NOD1 expression decreased during the progression of cervical intraepithelial neoplasia to cervical cancer and that HPV16 E6/E7 oncoproteins induced down-regulation of NOD1. Moreover, the activation of NOD1 promoted the apoptosis of HPV16-positive cervical cancer cells. The data indicated that the dysregulation of NOD1-mediated inflammation and apoptosis may contribute to cervical intraepithelial neoplasia progression and cervical cancer.

Highlights

Cervical cancer is the fourth most common cancer in women, with a high mortality rate [1]
We investigated the effect of nucleotide-binding oligomerization domain protein-1 (NOD1) on apoptosis of High-risk human papillomavirus (hrHPV)-infected cervical cancer cells
NOD1, an innate immune receptor, recognizes specific molecular patterns expressed on the cell walls of Gramnegative bacteria and initiates inflammatory response [12]

Summary

Introduction

Cervical cancer is the fourth most common cancer in women, with a high mortality rate [1]. High-risk human papillomavirus (hrHPV) persistent infection is considered the main risk factor for cervical cancer development [3]. In addition to HPV infection, other factors such as smoking and oral contraceptives may be related to the occurrence of cervical cancer [7]. Inflammation is another important risk factor in cervical cancer development [8, 9]. We investigated the expression of NOD1 in different grade cervical lesions, the impact of HPV infection on NOD1 expression, and the role of NOD1-mediated signaling in cervical cancer

Materials and methods

Result

Findings

Discussion