Comprehensive network analysis of dysregulated genes revealed MNX1-AS1/hsa-miR-4697-3p/HOXB13 axis in ovarian cancer chemotherapy response

Cancer Sci. 2022 Aug;113(8):2627-2641. doi: 10.1111/cas.15447. Epub 2022 Jun 24.

Abstract

Poor chemotherapy response is the main obstacle of ovarian cancer (OC) treatment. Platinum-refractory and -resistant patients are associated with a worse outcome than platinum-sensitive and partially sensitive patients, but the comprehensive similarities and differences among them are not yet clear. In this study, we analyzed the data of patients with different chemotherapy response in The Cancer Genome Atlas. We found a minority of altered genes were overlapped in refractory and resistant groups, as did the enriched pathways and Gene Ontology terms. We noticed that the neural signaling and drug metabolism enzymes were more significantly enriched and the protein-protein interaction supported these results. The transcription analysis highlighted PDX1 as the common and central transcription factor in both refractory and resistant groups. The competing endogenous RNA (ceRNA) network shared no common ceRNA pairs, indicating a major difference in noncoding RNA post-transcriptional regulation. In the end, we validated the expression, regulation, binding, and effect on chemotherapy response for selected MNX1-AS1/hsa-miR-4697-3p/HOXB13 in OC cell lines. Our study offered a novel and comprehensive insight into chemotherapy response, and potential targets for improving chemotherapy response in OC.

Keywords: HOXB13; MNX1-AS1; ceRNA; chemoresistance; miR-4697-3p; ovarian cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Humans
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • RNA, Long Noncoding* / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • HOXB13 protein, human
  • Homeodomain Proteins
  • MIRN4697 microRNA, human
  • MNX1 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors