Downregulated lncRNA UCA1 acts as ceRNA to adsorb microRNA-498 to repress proliferation, invasion and epithelial mesenchymal transition of esophageal cancer cells by decreasing ZEB2 expression

Cell Cycle. 2019 Sep;18(18):2359-2376. doi: 10.1080/15384101.2019.1648959. Epub 2019 Aug 6.

Abstract

Objective: Esophageal cancer (EC) is one of the most general malignant tumors in humans. There were few studies researching the connections between lncRNA UCA1 and EC. This study is to research the effect of lncRNA UCA1 adsorbing microRNA-498 (miR-498) as a ceRNA to regulate ZEB2 expression on epithelial mesenchymal transition (EMT), invasion and migration of EC cells. Methods: UCA1, miR-498 and ZEB2 expression in EC tissues and cells was detected by RT-qPCR or western blot analysis. EC cells were transfected with siRNA-UCA1, miR-498 mimics or their controls to determine cell colony, proliferation, cycle distribution, apoptosis, migration and invasion by colony formation assay, CCK-8 assay, flow cytometry, and Transwell assay, respectively. The protein expression of PCNA, c-Myc, E-cadherin, N-cadherin, MMP-2 and MMP-9 was detected by Western blot analysis. The growth rate and weight of transplanted tumor in nude mice were observed. Results: There were overly expressed UCA1 and ZEB2 and lowly expressed miR-498 in EC tissues and cells. LncRNA UCA1 acted as ceRNA to inhibit miR-498 expression and thereby increasing ZEB2 expression. With down-regulated UCA1 and up-regulated miR-498, ZEB2 expression, cell proliferation, colony formation, invasion, migration ability, EMT, tumor growth rate and weight in nude mice were apparently reduced. Conclusion: This study demonstrates that inhibited UCA1 up-regulated miR-498 and down-regulated ZEB2, thereby repressing proliferation activity, invasion, migration, and EMT of EC cells.

Keywords: LncRNA UCA1; MicroRNA-498; ZEB2.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics*
  • Epithelial-Mesenchymal Transition / genetics*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transfection
  • Tumor Burden / genetics
  • Zinc Finger E-box Binding Homeobox 2 / metabolism*

Substances

  • MIRN498 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • UCA1 RNA, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2

Grants and funding

There are currently no Funding Sources.