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The novel circCLK3/miR-320a/FoxM1 axis promotes cervical cancer progression

Hanqing Hong1,2, Hai Zhu1, Shujun Zhao1

  • 1Department of obstetrics and gynecology, The Third Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China.

Cell Death & Disease
|December 14, 2019
PubMed

Insights

Circular RNAs (circRNAs) are key in cancer. This study found circCLK3 is highly expressed in cervical cancer, promoting tumor growth and metastasis by sponging miR-320a and upregulating FoxM1.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, but their specific roles in cervical cancer remain largely unexplored.
  • Understanding the molecular mechanisms underlying cervical cancer progression is essential for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

  • To investigate the expression and function of circRNAs in cervical cancer.
  • To elucidate the role of circCLK3 in cervical cancer development, progression, and metastasis.
  • To clarify the molecular pathway involving circCLK3, miR-320a, and FoxM1 in cervical cancer.

Main Methods:

  • Differential expression analysis of circRNAs in cervical cancer tissues versus adjacent normal tissues.
  • In vitro and in vivo functional assays (cell proliferation, migration, invasion, tumorigenesis, metastasis) to assess circCLK3's role.
  • Molecular mechanism studies including pull-down, RNA immunoprecipitation (RIP), luciferase reporter, and rescue assays to determine interactions between circCLK3, miR-320a, and FoxM1.

Main Results:

  • circCLK3 expression was significantly elevated in cervical cancer tissues and correlated with tumor differentiation, FIGO stage, and stromal invasion depth.
  • Downregulation of circCLK3 inhibited cervical cancer cell growth and metastasis, while its upregulation promoted these processes both in vitro and in vivo.
  • circCLK3 directly sponges miR-320a, which in turn suppresses FoxM1 expression. circCLK3 promotes cervical cancer progression by inhibiting miR-320a and increasing FoxM1 levels.

Conclusions:

  • circCLK3 acts as an oncogenic circRNA in cervical cancer, promoting proliferation, migration, and invasion.
  • The circCLK3/miR-320a/FoxM1 axis represents a novel regulatory pathway in cervical cancer progression.
  • circCLK3 holds potential as a diagnostic biomarker and a therapeutic target for cervical cancer.

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