Coexpression of UCA1 and ITGA2 in pancreatic cancer cells target the expression of miR-107 through focal adhesion pathway

J Cell Physiol. 2019 Aug;234(8):12884-12896. doi: 10.1002/jcp.27953. Epub 2018 Dec 19.


Objectives: Abnormal expressions of microRNAs (miRNAs) are demonstrated in pancreatic cancer (PaC), but a major part of the mechanism remains elusive. This study mainly aimed to structure a coexpressed network of long noncoding RNA (lncRNA) and messenger RNA (mRNA) in PaC, as well as to explore their direct targets.

Methods: LncRNA and mRNA microarrays were used to determine the expression profiles in PaC cells. Analysis of Kyoto Encyclopedia of Genes and Genomes pathway was performed to identify pathways associated with differentially expressed mRNAs. Coexpression profiles were identified by constructing differentially expressed lncRNA-mRNA regulatory network and further validated by quantitative real-time polymerase chain reaction assay and western blot assay. The bioinformatics computational method was applied to predict the biological target of lncRNA and mRNA, which was identified by luciferase reporter assay. Migration/invasion ability and apoptosis rate of cells were assessed by transwell assay and flow cytometry assay.

Results: It was identified that the level of urothelial cancer associated 1 (UCA1) was increased in PaC cells, and the inhibition of UCA1 suppressed migration and invasion ability of the cancer cells. The luciferase reporter assay recognized that miR-107 was targeted by UCA1, and integrin subunit α 2 (ITGA2) was further targeted by miR-107. This confirmed the prediction of lncRNA-miRNA-mRNA regulation mechanism. In the regulatory pathways, UCA1 and ITGA2 promoted PaC progression via focal adhesion pathway related proteins such as ITGA3, SRC protooncogene/nonreceptor tyrosine kinase, protein tyrosine kinase 2, and AKT serine/threonine kinase 1.

Conclusion: The study revealed a regulatory network of UCA1-miR-107-ITGA2 and validated UCA1 and ITGA2 as potential prognostic factors for PaC.

Keywords: ITGA2; UCA1; lncRNAs; miR-107; pancreatic cancer cells.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / physiology
  • Focal Adhesions / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha2 / genetics*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Pancreatic Neoplasms / genetics*
  • RNA, Long Noncoding / genetics*


  • ITGA2B protein, human
  • Integrin alpha2
  • MIRN107 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • UCA1 RNA, human