OncoTargets and Therapy (Dec 2019)

MicroRNA-497-5p Induces Cell Cycle Arrest Of Cervical Cancer Cells In S Phase By Targeting CBX4

  • Chen Y,
  • Du J,
  • Wang Y,
  • Shi H,
  • Jiang Q,
  • Wang Y,
  • Zhang H,
  • Wei Y,
  • Xue W,
  • Pu Z,
  • Gao Y,
  • Li D,
  • Feng Y,
  • Yan J,
  • Zhang J

Journal volume & issue
Vol. Volume 12
pp. 10535 – 10545

Abstract

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Yani Chen,1,* Juan Du,1,* Yu Wang,1 Haiyan Shi,1 Qiuyu Jiang,1 Yangfeng Wang,1 Huahua Zhang,1 Yameng Wei,1 Wanjuan Xue,1 Zhiying Pu,2 Yi Gao,1 Dan Li,1 Yun Feng,1 Jing Yan,1 Jing Zhang1 1Department of Clinical Medicine, Medical College of Yan’an University, Yan’an 716000, People’s Republic of China; 2Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing ZhangDepartment of Clinical Medicine, Medical College of Yan’an University, No. 38, Guanghua Road, Yan’an 716000, Shaanxi Province, People’s Republic of ChinaTel +86-911-2412308Email [email protected]: miR-497-5p can inhibit cervical cancer cell proliferation. However, the underlying mechanism remains to be elucidated.Methods: Bioinformatics was used to analyze the target genes of miR-497-5p. qRT-PCR and Western blot were used to analyze mRNA and protein expression, respectively. Dual-luciferase reporter assay was used to analyze the direct binding between miR-497-5p and 3ʹ-untranslated region of CBX4. Cell viability was measured with MTT assay. Flow cytometry was performed to detect cell cycle distribution.Results: Here, using bioinformatics methods we firstly found that miR-497-5p regulated cervical carcinoma proliferation by targeting polycomb chromobox4 (CBX4). Expression of miR-497-5p in cervical carcinoma tissues was negatively correlated with CBX4. A binding region of miR-497-5p in 3ʹ-untranslated region of CBX4 was predicted. Further experiments confirmed that miR-497-5p directly targeted CBX4. Besides, RNA interference of CBX4 inhibited cervical cancer cell proliferation, arrested cells at S phase and reduced the expression of CDK2 and Cyclin A2 proteins. The use of miR-497-5p inhibitor compromised CBX4 interference RNAs induced cycle arrest of cervical cancer cells. Cells co-transfected with miR-497-5p inhibitors and CBX4 interference RNAs had a higher proliferation rate than CBX4 inference RNA-transfected cells.Conclusion: All together, the present study demonstrates that miR-497-5p inhibits cervical cancer cells proliferation by directly targeting CBX4.Keywords: MicroRNA-497-5p, CBX4, cervical cancer, carcinoma, proliferation

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