Hsa_circ_0006948 enhances cancer progression and epithelial-mesenchymal transition through the miR-490-3p/HMGA2 axis in esophageal squamous cell carcinoma

Aging (Albany NY). 2019 Dec 26;11(24):11937-11954. doi: 10.18632/aging.102519. Epub 2019 Dec 26.

Abstract

Increasing studies have indicated that circular RNAs (circRNAs) are important in cancer progression. However, few circRNAs associated with epithelial-mesenchymal transition (EMT) have been elucidated in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify whether hsa_circ_0006948 promotes ESCC cell EMT and explore its biological mechanisms. We first screened circRNA expression profiles using a circRNA microarray, and found that the expression of a novel circRNA, hsa_circ_0006948, is increased in 153 ESCC tissues and cell lines compared with noncancerous tissues and cell lines. Additionally, high hsa_circ_0006948 levels were positively associated with lymphatic metastasis and poor prognosis. Functionally, the assays indicated that cell proliferation, migration and invasion were promoted by hsa_circ_0006948 both in vitro and in vivo. Furthermore, we analyzed the relationship between hsa_circ_0006948 and miR-490-3p through bioinformatics, luciferase reporter assays, RNA immunoprecipitation and qRT-PCR. We found that hsa_circ_0006948 could bind directly to miR-490-3p which targets the 3'UTR of the oncogene HMGA2 to induce EMT. In conclusion, hsa_circ_0006948 was overexpressed in ESCC tissues and promoted cancer progression, and it could induce EMT by enhancing HMGA2 by sponging miR-490-3p, suggesting that hsa_circ_0006948 could be a biomarker for ESCC.

Keywords: EMT; HMGA2; circRNA; esophageal squamous cell carcinoma; hsa_circ_0006948.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Gene Expression Regulation, Neoplastic / genetics*
  • HMGA2 Protein / genetics
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • RNA, Circular / genetics*

Substances

  • HMGA2 Protein
  • HMGA2 protein, human
  • MIRN490 microRNA, human
  • MicroRNAs
  • RNA, Circular