Microarray expression profile and analysis of circular RNA regulatory network in malignant pleural effusion

Cell Cycle. 2018;17(24):2819-2832. doi: 10.1080/15384101.2018.1558860. Epub 2018 Dec 27.

Abstract

Malignant pleural effusion (MPE) is a common complication of lung cancer. Accumulating evidence has suggested that circular RNAs (circRNAs) play important roles in oncogenesis and progression of cancer. However, the expression pattern of circRNAs in MPE remains largely unknown and awaits investigation. The study was designed to elucidate the potential roles of differentially expressed circRNAs in MPE. Herein, we detected a total of 1350 differentially expressed circRNAs and 1727 differentially expressed mRNAs in lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) compared with tuberculous pleural effusion (TPE) by Clariom D Human Microarray. Among the top 5 up-regulated circRNAs (hsa_circ_0067705, hsa_circ_0025542, hsa_circ_0072793, hsa_circ_0084927, and hsa_circ_0085386), four were verified significantly up-regulated in LA-MPE by qRT-PCR and hsa_circ_0085386 had an increasing trend. CircRNA-miRNA-mRNA network for the top 5 up-regulated circRNAs was constructed and pathway analysis indicated that the enriched mRNA targets involved in PI3K-Akt signaling pathway, Axon guidance, Regulation of actin cytoskeleton and Rap1 signaling pathway were potentially regulated by these aberrantly expressed circRNAs. We generated specific circRNA profiles in LA-MPE for the first time. And analysis of circRNA regulatory network could provide evidence that circRNAs are important in MPE development because they participate in cancer-related pathways by sequestering miRNAs. Our findings suggested that aberrantly expressed circRNAs may be involved in the development of LA-MPE.

Keywords: Malignant pleural effusion; circRNA-miRNA-mRNA network; circular RNAs; functional enrichment; tuberculous pleural effusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cluster Analysis
  • Female
  • Gene Regulatory Networks*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / metabolism
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Pleural Effusion, Malignant / genetics
  • Pleural Effusion, Malignant / pathology*
  • Principal Component Analysis
  • RNA / metabolism*
  • RNA, Circular
  • RNA, Messenger / metabolism

Substances

  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger
  • RNA

Grants and funding

This work was supported by grants from the Science and Technology Commission Foundation of Tongzhou District, Beijing, China [KJ2017CX036-07].