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

Zhi-Hong Chen1,2, Ya-Jie Jing3, Jian-Bo Yu4

  • 1School of Basic Medicine, Youjiang Medical University for Nationalities, No. 98 Chengxiang Road, Baise 533000, China. chenzh808@126.com.

International Journal of Molecular Sciences
|August 1, 2019
PubMed

Insights

Epithelial splicing regulatory protein 1 (ESRP1) inhibits cervical cancer cell proliferation by reducing cyclin A2 mRNA stability, leading to G1-phase cell cycle arrest. This ESRP1/cyclin A2 pathway is a potential target for cervical cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Epithelial splicing regulatory protein 1 (ESRP1) is known to inhibit epithelial-to-mesenchymal transition (EMT) and regulate tumor metastasis.
  • The direct influence of ESRP1 on the cell cycle and its underlying molecular mechanisms remain unclear.

Purpose of the Study:

  • To investigate whether ESRP1 directly affects the cell cycle in cervical carcinoma.
  • To elucidate the molecular mechanisms by which ESRP1 influences cell proliferation and cell cycle progression.

Main Methods:

  • Correlation analysis between ESRP1 protein levels and Ki-67 proliferative index.
  • Assessment of ESRP1's effect on cervical carcinoma cell proliferation and cell cycle distribution (G1 arrest).
  • Investigation of ESRP1's impact on cyclin A2 mRNA stability and expression, and its binding to cyclin A2 mRNA 3'UTR.
  • Analysis of CDC20 expression in response to ESRP1 overexpression.

Main Results:

  • ESRP1 protein levels negatively correlated with the Ki-67 proliferative index (r = -0.521; p < 0.01).
  • ESRP1 overexpression inhibited cervical carcinoma cell proliferation and induced G1-phase arrest.
  • ESRP1 binds to the GGUGGU sequence in the 3'UTR of cyclin A2 mRNA, decreasing its stability.
  • ESRP1 overexpression enhanced CDC20 expression, promoting cyclin A2 degradation.

Conclusions:

  • ESRP1 overexpression induces G1-phase cell cycle arrest by reducing cyclin A2 mRNA stability.
  • ESRP1 inhibits cervical carcinoma cell proliferation through the ESRP1/cyclin A2 regulatory axis.
  • The ESRP1/cyclin A2 axis represents a potential therapeutic target for cervical cancer prevention and treatment.
Keywords:
ESRP1G1-phase arrestcell proliferationcyclin A2mRNA stability

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