Circ-HOMER1 enhances the inhibition of miR-1322 on CXCL6 to regulate the growth and aggressiveness of hepatocellular carcinoma cells

J Cell Biochem. 2020 Nov;121(11):4440-4449. doi: 10.1002/jcb.29672. Epub 2020 Feb 9.

Abstract

Hepatocellular carcinoma (HCC) is a common liver malignancy worldwide accompanying with the high rate of recurrence. Accumulating reports have documented the significance of circular RNAs (circRNAs) in carcinogenesis and development of HCC. This study aimed to establish the mechanism underlying circ-HOMER1 involvement in HCC. To this end, we identified a binding site for miR-1322 via bioinformatics, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and dual-luciferase reporter assays providing evidence of a direct link between circ-HOMER1 and miR-1322. Similarly, the target gene of miR-1322 was investigated. Moreover, we determined the specific function of circ-HOMER1 in HCC with the aid of qRT-PCR based on patient clinical records, Cell Counting Kit-8, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, and wound-healing and transwell assays. Notably, circ-HOMER1 was upregulated in both HCC cells and tissues. This aberrant expression pattern was closely correlated with larger tumor size, higher tumor-node-metastasis stage, and poorer prognosis for the patients with HCC. Moreover, silenced circ-HOMER1 inhibited cell proliferation, migration, and invasion concomitant with the promotion of apoptosis in HCC cells, and vice versa. Mechanistically, circ-HOMER1 enhanced the inhibition of miR-1322 on CXCL6 in HCC. Furthermore, we found that circ-HOMER1 promoted HCC cell growth and aggressiveness by miR-1322/CXCL6 axis. This study may provide a potential prognostic indicator and therapeutic target for patients with HCC.

Keywords: CXCL6; circ-HOMER1; circular RNA; hepatocellular carcinoma; miR-1322.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Movement
  • Cell Proliferation
  • Chemokine CXCL6 / genetics
  • Chemokine CXCL6 / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Homer Scaffolding Proteins / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Circular / genetics*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • CXCL6 protein, human
  • Chemokine CXCL6
  • HOMER1 protein, human
  • Homer Scaffolding Proteins
  • MIRN1322 microRNA, human
  • MicroRNAs
  • RNA, Circular