miR-203a-3p-DNMT3B feedback loop facilitates non-small cell lung cancer progression

Hum Cell. 2022 Jul;35(4):1219-1233. doi: 10.1007/s13577-022-00728-y. Epub 2022 Jun 7.

Abstract

It has been reported that microRNA-203a-3p (miR-203a-3p) modulates cell proliferation, migration and invasion in a variety of cancer cell types. However, little is known about its role in lung cancer progression. The present study found that miR-203a-3p was downregulated in non-small cell lung cancer (NSCLC) cell lines and tissues. Overexpression of miR-203a-3p inhibits NSCLC cell proliferation, migration and invasion, and promotes cellular apoptosis in vitro. Restoration of miR-203a-3p expression in A549 and NCI-H520 cells enhances their chemosensitivity. Further experiments showed that DNA methyltransferase 3B (DNMT3B) was a direct target of miR-203a-3p. In addition, the present results revealed that promoter hypermethylation was the potential mechanism responsible for low miR-203a-3p expression in NSCLC. Notably, feedback regulation between miR-203a-3p and DNMT3B was observed in NSCLC. Moreover, Overexpression of miR-203a-3p reduces tumor growth in vivo. In summary, the present study has identified an miR-203a-3p-DNMT3B feedback loop that facilitates NSCLC progression.

Keywords: DNA methyltransferase 3B; Methylation; Non-small cell lung cancer; microRNA-203a-3p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA (Cytosine-5-)-Methyltransferases* / genetics
  • DNA Methyltransferase 3B
  • Feedback
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • MicroRNAs* / genetics

Substances

  • MIRN203 microRNA, human
  • MicroRNAs
  • DNA (Cytosine-5-)-Methyltransferases