NUPR1 contributes to activate TFE3-dependent autophagy leading to cervical cancer proliferation

Abstract

Cervical cancer is a malignant tumor that occurs in the cervix of women and endangers their lives. In this study, we aimed to assess the roles of NUPR1 and TFE3 in cervical cancer. The Cancer Genome Atlas (TCGA) database was used to assess the correlation between NUPR1 and TFE3 expression in cervical cancer. By silencing NUPR1 and TFE3, and through 3-MA treatment, we determined whether their silencing could lead to lysosomal dysfunction, thereby inhibiting autophagy and cervical cancer cell proliferation. Their roles were further analyzed using molecular biological methods. Silencing NUPR1 and TFE3 inhibited cell proliferation and decreased the expression levels of autophagy-related genes, p62 and LC3B. By tracing lysosomes within cells, NUPR1 and TFE3 knockdown were found to induce lysosomal dysfunction, thereby inhibiting autophagy. In vivo experimental studies have shown that knockdown of NUPR1 and TFE3 can inhibit tumor growth, while reducing the ki67, p62, and LC3B expression levels and promoting apoptosis. Furthermore, the expression levels of lamp1 and lamp2, and the phosphorylation of PI3K (p-PI3K) and Akt (p-Akt) were significantly reduced after NUPR1 and TFE3 knockdown. However, treatment with 3-MA and overexpression of TFE3 could partially reverse the effect of silencing NUPR1. Overall, silencing NUPR1 reduced autophagy by inhibiting TFE3 in cervical cancer. Our results supply new evidence for the use of NUPR1 as a therapeutic target in cervical cancer.