Research Paper Volume 13, Issue 5 pp 7382—7396

Integrative analysis of exosomal microRNA-149-5p in lung adenocarcinoma

Wen Tian1, , He Yang1, , Baosen Zhou1,2, ,

  • 1 Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China
  • 2 Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China

Received: April 27, 2020       Accepted: November 15, 2020       Published: February 26, 2021      

https://doi.org/10.18632/aging.202596
How to Cite

Copyright: © 2021 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Exosomes play important roles in the regulation of various processes in the tumor microenvironment. In this study, we explored the mechanisms of exosomal miR-149-5p in the pathogenesis of lung adenocarcinoma. Raw data were downloaded and normalized using the R package. Significantly expressed exosomal miRNAs were subjected to co-expression network analysis. The proliferation and apoptotic abilities of tumor cells were assessed by the proliferation and apoptosis assays. Univariate and multivariate analyses were performed to identify the independent risk factors of exosomal miR-149-5p and AMOTL2. Results showed that exosomal miR-149-5p was enriched in peripheral serum and tumor cells. The upregulation of exosomal miR-149-5p promoted the growth of tumor cells and inhibited apoptosis of tumor cells. Notably, AMOTL2, the target gene of exosomal miR-149-5p, was significantly downregulated in lung adenocarcinoma and may be considered as an independent risk factor of poor survival. In lung adenocarcinoma cells, AMOTL2 downregulation reversed the promoting effect of miR-149-5p on A549 cells growth and the inhibition effect of miR-149-5p on A549 cells apoptosis. Collectively, these results provide specific insights for further mechanistic studies on lung adenocarcinoma.

Abbreviations

AUC: Area under curve; BMMSC: Bone marrow mesenchymal stem cells; CI: Confidence Interval; FBS: Fetal calf serum; GEO: Gene expression omnibus; GSEA: Gene-set enrichment analysis; LUAD: Lung adenocarcinoma; HR: Hazard ratio; MUT: Mutant type; NC: Negative control; NSCLC: Non-small cell lung cancer; OD: Optical density; PBS: Phosphate buffer solution; PVDF: Polyvinylidene fluoride; ROC: Receiver Operating Characteristic; RPM: Reads of exon model per Million mapped reads; RT-PCR: Reverse transcription-polymerase chain reaction; TCGA: The Cancer Genome Atlas; THPA: The human protein atlas; UTR: Untranslated region; WGCNA: Weighted gene co-expression network analysis; WT: Wild type.