miR‑302c‑3p and miR‑520a‑3p suppress the proliferation of cervical carcinoma cells by targeting CXCL8

Mol Med Rep. 2021 May;23(5):322. doi: 10.3892/mmr.2021.11961. Epub 2021 Mar 24.

Abstract

The aim of the present study was to identify the differentially expressed microRNAs (miRs) in cervical carcinoma (CC) tissues and cells and to explore the function of miR‑302c‑3p and miR‑520a‑3p in the proliferation of CC cells. Potential dysregulated miRNAs in CC tissues and tumour‑adjacent tissues were detected. Reverse transcription‑quantitative PCR (RT‑qPCR) was performed to determine the expression of miR‑302c‑3p, miR‑520a‑3p and CXCL8 in CC tissues and cell lines. The target genes of the miRNAs were predicted using miRTarBase and verified by luciferase reporter assays. RT‑qPCR and western blotting were performed to measure the expression of C‑X‑C motif ligand (CXCL)8 after transfection. The effect on proliferation was verified by Cell Counting Kit assay and ethynyl‑2‑deoxyuridine staining. Flow cytometry was utilised to assess the effect on apoptosis. In the present study, miR‑302c‑3p and miR‑520a‑3p were markedly downregulated in CC cell lines compared to the normal cervical cell line H8. Functionally, overexpression of miR‑302c‑3p and/or miR‑520a‑3p inhibited proliferation and promoted the apoptosis of CC cell lines in vitro, while the knockdown of miR‑302c‑3p and/or miR‑520a‑3p had the opposite effect. Furthermore, miR‑302c‑3p and miR‑520a‑3p could both bind to CXCL8. Inhibition of CXCL8 in combination with miR‑302c‑3p and/or miR‑520a‑3p overexpression exerted proliferation‑suppressive and apoptosis‑stimulating effects on CC cells, whereas restoring CXCL8 attenuated the miR‑302c‑3p‑ and miR‑520a‑3p‑induced anti‑proliferative and pro‑apoptotic effects. miR‑302c‑3p and miR‑520a‑3p suppress the proliferation of CC cells by downregulating the expression of CXCL8, which may provide a novel target for the treatment of CC.

Keywords: cervical carcinoma; miR‑302c‑3p; miR‑520a‑3p; C‑X‑C motif ligand 8; proliferation; apoptosis.

MeSH terms

  • Adult
  • Aged
  • Antagomirs / pharmacology
  • Apoptosis / genetics
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Interleukin-8 / genetics*
  • MicroRNAs / genetics*
  • Middle Aged
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antagomirs
  • CXCL8 protein, human
  • Interleukin-8
  • MicroRNAs

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant no. 81672560).