ESRP1 Induces Cervical Cancer Cell G1-Phase Arrest Via Regulating Cyclin A2 mRNA Stability

Abstract

Accumulating evidence indicates that epithelial splicing regulatory protein 1 (ESRP1) can inhibit the epithelial-to-mesenchymal transition (EMT), thus playing a central role in regulating the metastatic progression of tumors. However, it is still not clear whether ESRP1 directly influences the cell cycle, or what the possible underlying molecular mechanisms are. In this study, we showed that ESRP1 protein levels were significantly correlated with the Ki-67 proliferative index (r = −0.521; p < 0.01), and that ESRP1 overexpression can significantly inhibit cervical carcinoma cell proliferation and induced G1-phase arrest by downregulating cyclin A2 expression. Importantly, ESRP1 can bind to GGUGGU sequence in the 3′UTR of the cyclin A2 mRNA, and ESRP1 overexpression significantly decreases the stability of the cyclin A2 mRNA. In addition, our experimental results confirm that ESRP1 overexpression results in enhanced CDC20 expression, which is known to be responsible for cyclin A2 degradation. This study provides the first evidence that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA, and inhibits cervical carcinoma cell proliferation. The findings suggest that the ESRP1/cyclin A2 regulatory axis may be essential as a regulator of cell proliferation, and may thus represent an attractive target for cervical cancer prevention and treatment.

Proteomics-Based Evidence for a Pro-Oncogenic Role of ESRP1 in Human Colorectal Cancer Cells

“…An increasing number of studies describe ESRP1 as an oncogenic RBP [28,29]. In a recent review by Garcia-Cardenas et al ESRP1 was described as one of the 35 RBPs (out of a total of 1393 RBPs) bearing an oncogenic role in CRC [30].…”

Eight Aging-Related Genes Prognostic Signature for Cervical Cancer

“…miR-140-5p knockdown reverses small interfering RNA-FEN1-mediated suppressive effects on CC cell phenotypes, potentially via triggering cell cycle arrest at the G1 phase [ 82 ]. Epithelial splicing regulatory protein 1 (Esrp1) overexpression induces G1-phase cell cycle arrest by downregulating cyclin A2 expression and inhibits the proliferation of cervical carcinoma cells [ 83 ].…”

Thymidine Kinase 1 Mediates the Synergistic Antitumor Activity of Ubenimex and Celecoxib via Regulation of Cell Cycle in Colorectal Cancer

“…The G1, S, G2, and M phases control programmed cell proliferation. Cell cycle checkpoints (G1, G2, and intermediate (M) or spindle checkpoints) and the order activation of cyclin-dependent kinases (CDKs) are needed during cell cycle transition-and ensure that the DNA replicates correctly so that the cell is ready to divide (Chen et al, 2019).…”