SNAI2 enhances HPV‑negative cervical cancer cell dormancy by modulating u‑PAR expression and the activity of the ERK/p38 signaling pathway in vitro.

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The prognosis of patients with human papillomavirus (HPV)‑negative cervical cancer is significantly worse than that of patients with HPV‑positive cervical cancer. Understanding the mechanisms of this is crucial for preventing disease evolution. In the present study, the GV367‑snail family transcriptional repressor 2 (SNAI2) lentiviral vector was constructed and transduced into C‑33A cells. Subsequently, the proliferation of tumor cells was detected using the Cell Counting Kit (CCK)‑8 method. Flow cytometry was used to analyze the cell cycle progression of tumor cells. The glucose consumption of tumor cells was detected using an oxidase assay, and the senescence of tumor cells was detected using beta‑galactosidase staining. The gene expression and the activity of p38 and ERK1/2 were detected using reverse transcription‑quantitative PCR and western blotting, respectively. The C‑33A‑SNAI2 cell line was successfully established. Compared with HeLa and C‑33A‑Wild cells, the proliferation and percentage of G0/G1‑phase cells in the C‑33A‑SNAI2 group were decreased, as detected by the CCK‑8 assay (100±0 vs. 239.1±58.3 vs. 39.7±20.1, P<0.01) and flow cytometry (34.0±7.1% vs. 46.2±10.6% vs. 61.3±5.3%, P<0.05). Compared with the HeLa group, the glucose consumption of the C‑33A‑Wild and C‑33A‑SNAI2 groups was significantly decreased (P<0.01). The results of beta‑galactosidase staining showed that the proportion of beta‑galactosidase‑positive cells in the C‑33A‑SNAI2 group was significantly decreased compared with the C‑33A‑Wild group (P<0.01). Upregulation of SNAI2 enhanced the increase in p21 expression, and the decrease in CDK1, urokinase plasminogen activator receptor (u‑PAR) and cyclin D1 expression in C‑33A cells compared with C‑33A‑Wild cells (P<0.05). In addition, the activities of p38, ERK1/2 and the phosphorylated (p)‑ERK1/2/p‑p38 ratio were decreased in the C‑33A‑SNAI2 group compared with the C‑33A‑Wild and HeLa groups (P<0.05). In conclusion, SNAI2 enhanced HPV‑negative cervical cancer C‑33A cell dormancy, which was characterized by G0/G1 arrest, by the downregulation of u‑PAR expression, and a decrease in the activity of the p‑ERK1/2 and p‑p38MAPK signaling pathways in vitro. Cancer recurrence and metastases are responsible for most cancer‑related deaths. Given that SNAI2 is required for enhancing HPV‑negative cervical cancer cell dormancy, regulating this process may promote cervical tumor cells to enter a continuous dormant state, which could be a potential approach for tumor therapy.