MAPKAPK5-AS1/miR-515-5p/CAB39 Axis Contributes to Non-small Cell Lung Cancer Cell Proliferation and Migration

Mol Biotechnol. 2023 Nov;65(11):1887-1897. doi: 10.1007/s12033-023-00654-w. Epub 2023 Mar 3.

Abstract

Several studies have elucidated the pivotal function that long noncoding RNAs (lncRNAs) exerted on the initiation and development of various human carcinomas, encompassing non-small cell lung cancer (NSCLC). In spite of the fact that lncRNA MAPKAPK5 antisense RNA 1 (MAPKAPK5-AS1) has already been investigated by researchers and confirmed to play oncogenic roles in colorectal cancer, the underlying regulatory function of MAPKAPK5-AS1 in NSCLC cells still remain unclear. In our research, we found that MAPKAPK5-AS1 was expressed at high levels in NSCLC cells. Biological functional assays unclosed that downregulation of MAPKAPK5-AS1 repressed proliferative and migratory capacities whereas promoted apoptotic level in NSCLC cells. Molecular mechanism experiments confirmed that, in NSCLC cells, MAPKAPK5-AS1 combined with miR-515-5p and negatively modulated miR-515-5p expression level. Besides, calcium-binding protein 39 (CAB39) expression level was verified to be negatively modulated by miR-515-5p whereas positively modulated by MAPKAPK5-AS1 in NSCLC cells. Furthermore, rescued-function assays disclosed that inhibited miR-515-5p expression or overexpressed CAB39 could restore the suppressive influence of MAPKAPK5-AS1 silence on NSCLC progression. In summary, MAPKAPK5-AS1 upregulates CAB39 expression level to facilitate NSCLC progression by sequestering miR-515-5p, providing promising biomarkers for NSCLC treatment.

Keywords: CAB39; MAPKAPK5-AS1; NSCLC; miR-515-5p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • MicroRNAs
  • MAP-kinase-activated kinase 5
  • MIRN515 microRNA, human