Downregulated miR-18a and miR-92a synergistically suppress non-small cell lung cancer via targeting Sprouty 4

Bioengineered. 2022 Apr;13(4):11281-11295. doi: 10.1080/21655979.2022.2066755.

Abstract

As a novel noncoding RNA cluster, miR-17-92 cluster include six members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a. Dysregulation of miR-17-92 has been proved to be connected with the advancement of a series of human diseases, but the roles of miR-17-92 cluster in non-small cell lung cancer (NSCLC) have not been absolutely elaborated. Herein, we determined that miR-17-92 cluster were upregulated significantly in NSCLC tissues, and the cell proliferation, migration and cycle progression of NSCLC were also facilitated under the function of miR-17-92 cluster. Sprouty 4 (SPRY4) was a direct target of miR-92a, and its overexpression restrained the exacerbation of NSCLC induced by miR-92a. Furthermore, the tumor xenograft assay showed that miR-92a facilitated tumor growth by inhibiting the expression of SPRY4 and mediating Epithelial-Mesenchymal Transition (EMT) in vivo. Finally, we looked into the synergistic effects of miR-92a and miR-18a on NSCLC, and found that antagomiR-18a treatment arrested the tumor growth rate of xenografted mice markedly.

Keywords: NSCLC; SPRY4; miR-18a; miR-92a.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • Mice
  • MicroRNAs* / metabolism

Substances

  • MIRN18A microRNA, human
  • MicroRNAs

Grants and funding

The financial supports of this study were obtained from the National Natural Science Foundation of China (No. 81572122) and Shanghai Science and Technology Committee (No.20S11901300).