Effect of NQO1 Downregulation on the Migration and Invasion of HPV16-Positive Cervical Cancer Cells.

Abstract

Objective: This study aimed to identify upregulated genes in HPV16-positive cervical cancer cells and investigate the impact of downregulating NAD(P) H:quinone oxidoreductase 1 (NQO1) on the survival of these cells.

Methods: Transcriptomic sequencing (RNA-seq) was utilized to pinpoint upregulated genes and associated cancer-related pathways in HPV16-positive cervical cancer cells, comparing them to HPV-negative cervical cancer cells. NQO1 gene knockdown was performed in HPV16-positive cervical cancer cell lines to assess its effect on cell survival, including parameters such as cell proliferation, migration, invasion, cell cycle progression, apoptosis, and the expression of key proteins in the PI3K/AKT pathway, p53, and RECK.

Results: Genes with a fold change ≥4.0 in HPV16-positive cervical cancer cell lines were predominantly localized to the extracellular region and plasma membrane. These genes were involved in protein binding and cell adhesion, influencing cellular responses to stimuli and tissue development. KEGG pathway analysis identified the most significant pathways, including metabolic pathways, cancer pathways, MAPK signaling, and PI3K-AKT signaling. Knockdown of NQO1 significantly decreased cell proliferation, migration, and invasion, while increasing apoptosis in HPV16-positive cervical cancer cells (p ≤ 0.01). Additionally, proteins associated with the PI3K-AKT pathway were downregulated, while p53 and RECK protein levels were elevated.

Conclusion: Our findings suggest that NQO1 plays a crucial role in promoting migration and invasion in HPV16-positive cervical cancer cells, highlighting its potential as a therapeutic target.