Circular RNA hsa_circ_0002360 promotes non-small cell lung cancer progression through upregulating matrix metalloproteinase 16 and sponging multiple micorRNAs

Bioengineered. 2021 Dec;12(2):12767-12777. doi: 10.1080/21655979.2021.1999370.

Abstract

Dysregulated circular RNAs (circRNAs) are involved in the progression of non-small cell lung cancer (NSCLC). However, the role of has_circ_0002360 (circ_0002360) in NSCLC has rarely been reported. In this study, circ_0002360 expression in NSCLC tissues and cell lines was measured using microarray data and quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function, cell models were established; 5-bromo-2-deoxyuridine (BrdU) and transwell assays were conducted to detect NSCLC cell growth, migration, and invasion. What is more, bioinformatic analysis and dual-luciferase reporter assay were adopted to show how circ_0002360, microRNAs (miR-127-5p, miR-145-5p, miR-585-3p, and miR-758-3p), and matrix metalloproteinase 16 (MMP16) 3'UTR interact with each other. Western blotting was executed to probe the regulatory effects of circ_0002360 and these miRNAs on MMP16 protein expression in NSCLC cells. We found that circ_0002360 expression was raised in NSCLC tissues. High circ_0002360 expression predicted a short overall survival time for NSCLC patients. Circ_0002360 overexpression promoted NSCLC cell proliferative, migrative, and invasive abilities, and circ_0002360 depletion worked oppositely. MiR-127-5p, miR-145-5p, miR-585-3p, and miR-758-3p were the targets of circ_0002360, and circ_0002360 could regulate MMP16 expression by competitively binding with the above miRNAs. In summary, circ_0002360 serves as a competitive endogenous RNA to raise MMP16 expressions by competitively binding to miR-127-5p, miR-145-5p, miR-585-3p, and miR-758-3p, thereby promoting NSCLC progression.

Keywords: Non-small cell lung cancer; circ_0002360; matrix metalloproteinase 16; microRNAs.

MeSH terms

  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Matrix Metalloproteinase 16 / genetics*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Up-Regulation / genetics*

Substances

  • MicroRNAs
  • RNA, Circular
  • Matrix Metalloproteinase 16

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.