Cancer-released exosomal circular RNA circ_0008717 promotes cell tumorigenicity through microRNA-1287-5p/P21-activated kinase 2 (PAK2) axis in non-small cell lung cancer

Bioengineered. 2022 Apr;13(4):8937-8949. doi: 10.1080/21655979.2022.2056822.

Abstract

Circular RNA (circRNA) circ_0008717 has been revealed to promote cell carcinogenesis in non-small cell lung cancer (NSCLC). Exosomal circRNA packaged into exosomes has been defined as a potential diagnostic and therapeutic biomarker of cancers. However, little attention is focused on the role of circRNAs within exosomes in NSCLC. Exosomes were isolated by ultracentrifugation method and qualified by nanoparticle tracking analysis and Western blot. Levels of circ_0008717, microRNA (miR)-1287-5p, and P21-activated kinase 2 (PAK2) were detected using qRT-PCR and western blot. The interaction between miR-1287-5p and circ_0008717 or PAK2 was investigated. The phenotypes of NSCLC cells with circ_0008717 downregulation were tested. Circ_0008717 was highly expressed in NSCLC. Functionally, circ_0008717 deficiency suppressed cell malignant phenotypes in NSCLC in vitro and in nude mice. Circ_0008717 sponged miR-1287-5p to elevate PAK2, a downstream target of miR-1287-5p. Silencing of miR-1287-5p blocked the antitumor effects of circ_0008717 knockdown in NSCLC cells. Besides, miR-1287-5p repressed cell oncogenic behaviors in NSCLC by targeting PAK2. Besides that, we confirmed that circ_0008717 was incorporated into exosomes in NSCLC cells. Circ_0008717 knockdown inhibited NSCLC tumorigenesis via miR-1287-5p/PAK2 axis, and the extracellular circulating circ_0008717 was transferred through incorporation in exosomes.

Keywords: Exosomes; NSCLC; PAK2; circ_0008717; miR-1287-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Proliferation / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • p21-Activated Kinases* / genetics

Substances

  • MIRN1287 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • PAK2 protein, human
  • p21-Activated Kinases

Grants and funding

This work was supported by Tianjin-funded Key Construction Protects-Specialized Subject of Clinical Laboratory Medicine, Tianjin First Center Hospital (2019CM16) and Key Project of Tianjin Natural Science Foundation (18JCZDJC98500).