Exosomal circ_0048856 derived from non-small cell lung cancer contributes to aggressive cancer progression through downregulation of miR-1287-5p

Pathol Res Pract. 2022 Apr:232:153659. doi: 10.1016/j.prp.2021.153659. Epub 2021 Oct 16.

Abstract

Aim: Present study was aimed to explore the diagnostic value and mechanism of exosome derived circular RNA (circ)_0048856 in non-small cell lung cancer (NSCLC) development.

Methods: Exosomes protein markers, CD63 and CD9, were examined by Western blot. Real time quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR) was used to detect the relative expression of circ_0048856 and miR-1287-5p. Proliferation of NSCLC cell was detected by MTT assay. Transwell assay was utilized to evaluated the migration and invasion of NSCLC cells. Apoptosis rate was examined by Flow cytometry. Double luciferase report assay was used to assess the targeting association between circ_0048856 and miR-1287-5p. Diagnostic value of circ_0048856 for NSCLC was estimated by receiver operating characteristic (ROC) curve. Animal models were constructed to explore the function of exosomal circ_0048856 in NSCLC.

Results: Diameter of exosomes in NSCLC serum was ranged between 75 and 150 nm. Exosomes circ_0048856 was enhanced in NSCLC serum and cell lines (P < 0.001). Exosome derived circ_0048856 had high diagnostic value for NSCLC. Area under the curve (AUC) was 0.943 (95%CI=0.904-0.982, P < 0.001). at the optimal cutoff value of 1.800, the sensitivity was 0.880, and specificity was 0.800. Exosome circ_0048856 facilitated proliferation, migration and invasion, inhibited apoptosis of NSCLC cells. MiR-1287-5p could be effaced by circ_0048856. MiR-1287-5p reversed the biological behavior changes of NSCLC cells which induced by circ_0048856. In vivo, exosomal circ_0048856 could significantly promote tumor growth (P < 0.001).

Conclusion: Exosomes derived circ_0048856 was elevated in NSCLC serum and cell lines. Exosome circ_0048856 promoted the NSCLC development by targeting miR-1287-5p. Exosome circ_0048856 had high diagnostic value for NSCLC.

Keywords: Circ_0048856; Diagnosis; Exosome; MiR-1287–5p; Non-small cell lung cancer.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Proliferation / genetics
  • Down-Regulation
  • Humans
  • Lung Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Circular / genetics

Substances

  • MIRN1287 microRNA, human
  • MicroRNAs
  • RNA, Circular