MZF1 Transcriptionally Activated MicroRNA-328-3p Suppresses the Malignancy of Stomach Adenocarcinoma via Inhibiting CD44

J Immunol Res. 2022 May 28;2022:5819295. doi: 10.1155/2022/5819295. eCollection 2022.


MicroRNA-328-3p (miR-328-3p) plays a critical role in mediating the progression of multiple types of cancers. To date, no study has concentrated on the molecular mechanism of miR-328-3p in mediating stomach adenocarcinoma (STAD). In this study, it was found that miR-328-3p was downregulated in STAD, and inhibition of miR-328-3p significantly promoted the growth, migration, invasion, and stemness of STAD cells, while miR-328-3p overexpression exerted reverse effects. Through bioinformatics analysis, it was uncovered that a cluster of differentiation 44 (CD44) was upregulated in STAD and closely associated with the prognosis of STAD patients. Mechanistically, we identified CD44 as the target gene of miR-328-3p. Notably, knockdown of CD44 abolished the promoting function of miR-328-3p inhibitor in the development of STAD. Moreover, myeloid zinc finger protein 1 (MZF1) was confirmed as an upstream transcription factor for miR-328-3p, which is involved in enhancing miR-328-3p expression. In addition, the role of MZF1 downregulation in the malignant traits of STAD cells was blocked by miR-328-3p overexpression. More importantly, upregulation of miR-328-3p efficiently suppressed STAD tumor growth in vivo. Collectively, our findings illustrated that MZF1-mediated miR-328-3p acted as a cancer suppressor in STAD progression via regulation of CD44, which suggested the possibility of the MZF1/miR-328-3p/CD44 axis as a novel promising therapeutic candidate for STAD.

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Stomach Neoplasms* / pathology


  • CD44 protein, human
  • Hyaluronan Receptors
  • Kruppel-Like Transcription Factors
  • MIRN328 microRNA, human
  • MZF1 protein, human
  • MicroRNAs