Effects of miR-330 restoration on pancreatic cancer cells oncogenesis

Pathol Res Pract. 2024 Jun:258:155337. doi: 10.1016/j.prp.2024.155337. Epub 2024 May 3.

Abstract

Background: Inappropriate expressions of various miRNAs have reported in different human malignancies. Evidence suggested that miR-330 may play as both onco-miR and/or tumor suppressor-miR in different cancers. In the present study, we evaluated effects of miR-330 on proliferation and migration of pancreatic cancer (PC) cells as well as underlying molecular mechanisms.

Design: The expression of miR-330 was evaluated in clinical tissue samples of patients with PC. Transfection of the PC cells (PANC-1) by miR-330 was conducted by pCMV vector. The cancer-related genes expression was investigated in mRNA and protein level following transfection of the PC cells. Furthermore, the PC cells viability, invasion, migration, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle profile were investigated after transfection by miR-330.

Results: The results indicated that expression of miR-330 downregulated in patients with PC. Stable increase of miR-330 expression after transfection in PC cells reduces viability, mitochondrial membrane potential, invasion, and migration. Further assessments demonstrated that upregulation of miR-330 increases apoptosis and autophagy percentage in the PC cells. Moreover, a cell cycle arrest was observed in G1, Sub-G1, and S phases following transfection of the PC cells. These findings can be explained by modified mRNA and protein expression of apoptosis- and metastasis-related genes.

Conclusion: Our study suggested that miR-330 acts as a tumor suppressor in PC cells, and revealed that upregulation of miR-330 may provide an effective therapeutic approach for overcoming progression and metastasis in patients with PC.

Keywords: Apoptosis; Metastasis; MiR-330; Pancreatic cancer; Proliferation.

MeSH terms

  • Apoptosis* / genetics
  • Autophagy / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • Male
  • Membrane Potential, Mitochondrial / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology

Substances

  • MicroRNAs
  • MIRN330 microRNA, human