Knockdown of CENPU inhibits cervical cancer cell migration and stemness through the FOXM1/Wnt/β-catenin pathway

Tissue Cell. 2023 Apr:81:102009. doi: 10.1016/j.tice.2022.102009. Epub 2022 Dec 24.

Abstract

Currently, the clinical outcome of cervical cancer (CC) is still undesirable, and it is urgent to explore more treatment strategies for CC. In this study, the effects of CENPU on migration and stemness of CC was studied. The CENPU expression were retrieved from The Cancer Genome Atlas (TCGA). The effects of CENPU on the viability and proliferation of cells were evaluated by CCK-8 assay and colony formation assay. Wound healing assay and invasion assay were chosen to assess migration and invasion of cells. Tumorsphere-forming assay was applied for testing the stemness. Western blot analysis was applied for assessing the level of CENPU, Nanog, Oct4, FOXM1, β-catenin, c-myc and MMP-7. The tumor sizes and volumes were also measured. The TCGA data and WB assay suggested that CENPU was upregulated in CC. CENPU knockdown would inhibit the viability of CC cells and prohibit the migration and invasion of cells. Tumorsphere-forming assay and WB results suggested that CENPU silencing decreased the sphere formation rate and the expression of Nanog and Oct4. Moreover, CENPU knockdown suppressed the expression of FOXM1, β-catenin, c-myc and MMP-7 by WB. In vivo study demonstrated that CENPU knockdown inhibited the growth of CC, indicated by reduced sizes and volumes of CC. In summary, our results suggested that knockdown of CENPU inhibited CC migration and stemness through the FOXM1/Wnt/β-catenin pathway.

Keywords: CENPU; Cervical cancer; FOXM1/Wnt/β-catenin pathway; Migration; Stemness.

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation / genetics
  • Chromosomal Proteins, Non-Histone* / genetics
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Female
  • Forkhead Box Protein M1* / genetics
  • Forkhead Box Protein M1* / metabolism
  • Forkhead Box Protein M1* / pharmacology
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Matrix Metalloproteinase 7 / genetics
  • Matrix Metalloproteinase 7 / metabolism
  • Matrix Metalloproteinase 7 / pharmacology
  • Neoplastic Stem Cells / metabolism
  • Uterine Cervical Neoplasms* / pathology
  • Wnt Signaling Pathway / genetics
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • beta Catenin
  • Forkhead Box Protein M1
  • FOXM1 protein, human
  • Matrix Metalloproteinase 7
  • CENPU protein, human
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone