Activation of COL11A1 by PRRX1 promotes tumor progression and radioresistance in ovarian cancer

Int J Radiat Biol. 2021;97(7):958-967. doi: 10.1080/09553002.2021.1928780. Epub 2021 May 25.

Abstract

Purpose: Although radiotherapy is a common treatment option for all kinds of cancer patients, including ovarian cancer, a major obstacle limiting its application in the development of resistance. Therefore, it is urgently needed to clarify the mechanism of radiosensitivity modulation.

Materials and methods: We obtained open datasets and analyzed the expression of collagen type XI alpha 1 (COL11A1) in ovarian cancer patients with different stages. Meanwhile, the correlation of COL11A1 and survival outcomes is determined by Kaplan-Meier analysis. The role of COL11A1 in cell proliferation was observed in an in vitro knockdown system. SKOV3 radioresistant cells were established to determine the role of COL11A1 on radioresistant in ovarian cancer.

Results and discussion: COL11A1 were highly enriched in late-stage ovarian cancer tumor tissues and negatively correlated with survival outcomes in ovarian cancer. The functional analysis found that COL11A1 promoted ovarian cancer cell proliferation in vitro. Importantly, COL11A1 decreased radiosensitivity in ovarian cancer by AKT activation. Paired related homeobox 1 (PRRX1) acted as an upstream transcription factor to regulate COL11A1 expression in ovarian cancer. Increased COL11A1 expression is related to low survival outcomes and radiosensitivity in ovarian cancer.

Conclusions: Targeting COL11A1 is a promising strategy for improving radiotherapy efficiency.

Keywords: Akt; COL11A1; PRRX1; Radioresistance; ovarian cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation* / radiation effects
  • Collagen Type XI* / genetics
  • Collagen Type XI* / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Humans
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Ovarian Neoplasms* / radiotherapy
  • Radiation Tolerance* / genetics

Substances

  • COL11A1 protein, human
  • Collagen Type XI
  • PRRX1 protein, human
  • Homeodomain Proteins