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

Abstract

Purpose: 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 3'-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 3'-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: CBX4; MicroRNA-497-5p; carcinoma; cervical cancer; proliferation.