MiR-766-3p Inhibit the Proliferation, Stemness, and Cell Cycle of Pancreatic Cancer Cells Through the MAPK/ERK Signaling Pathway

Mol Genet Genomic Med. 2024 Dec;12(12):e70049. doi: 10.1002/mgg3.70049.

Abstract

Background: As a commonly identified cancer in clinics, pancreatic cancer (PC) has poor prognostic outcomes. This work focused on clarifying the association between MIR-766-3P expression and PC development and progression, as well as the possible role as a biomarker in PC.

Methods: MIR-766-3P expression within the human PC cells and samples was measured through miRNA RT-PCR. The gene levels regulated by MIR-766-3P were analyzed through western blot (WB) and qRT-PCR. To analyze whether MIR-766-3P was of certain significance in in vitro and in vivo PC cell proliferation, stemness, and cell cycle progression, the gain/loss-of-function assays were performed. Bioinformatics, RNA sequencing (RNA-seq), and luciferase reporter assay were conducted for exploring regulatory role of MIR-766-3P/MAPK1/MAPK/ERK signal axis in PC.

Result: In comparison with the normal controls, MIR-766-3P expression markedly decreased the tissues and cells of PC. Furthermore, MIR-766-3P could remarkably inhibit the proliferation, stemness, cell cycle progression, and development of PC. The analyses using RNA-seq, and dual-luciferase examination showed that MIR-766-3P could directly target mitogen-activated protein kinase 1 (MAPK1). According to Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, MIR-766-3P could affect PC malignant phenotype by MAPK1 and the regulation of the MAPK/ERK-related pathway.

Conclusion: MIR-766-3P has a certain impact on PC malignant phenotype through combining with MAPK1 while regulating MAPK/ERK-related pathway in vitro and in vivo.

Keywords: MAPK/ERK; MAPK1; MIR‐766‐3P; pancreatic cancer.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology

Substances

  • MicroRNAs
  • MIRN766 microRNA, human
  • Mitogen-Activated Protein Kinase 1
  • MAPK1 protein, human