LncRNA MAFG-AS1 promotes the malignant phenotype of ovarian cancer by upregulating NFKB1-dependent IGF1

Cancer Gene Ther. 2022 Mar;29(3-4):277-291. doi: 10.1038/s41417-021-00306-8. Epub 2021 May 25.

Abstract

Long non-coding RNAs (lncRNAs) were recently recognized to vitally function in a variety of cancer cellular events, including epithelial-mesenchymal transition (EMT), invasion, and migration, particularly in ovarian cancer (OC). Herein, we sought to investigate the potential role of MAFG-AS1 in the malignant behaviors of OC cells. The binding affinity between MAFG-AS1, miR-339-5p, NFKB1 or IGF1 was characterized so as to identify the underlying mechanism of corresponding their interactions. We conducted MAFG-AS1 overexpression or knockdown along with NFKB1 and IGF1 silencing to examine their effects on the EMT, migration, and invasion of OC cells. Tumors were xenografted in nude mice to validate the in vitro findings. Our data showed significantly high expression pattern of MAFG-AS1 in the OC tissues and cells. Further mechanistic investigations revealed that MAFG-AS1 upregulated the IGF1 expression pattern through recruitment of NFKB1, whereas MAFG-AS1 upregulated the NFKB1 expression pattern through binding to miR-339-5p. Thus, MAFG-AS1 overexpression accelerated the EMT, invasion, and migration of OC cells, which could be annulled by silencing of IGF1 or NFKB1. Besides, our in vitro findings were successfully recapitulated in the xenograft mice. These results determined that MAFG-AS1 stimulated the OC malignant progression by upregulating the NFKB1-mediated IGF1 via miR-339-5p, thus highlighting a novel potential therapeutic target against OC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor I
  • MafG Transcription Factor / genetics
  • MafG Transcription Factor / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B p50 Subunit
  • Neoplasm Invasiveness / genetics
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Phenotype
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Repressor Proteins / genetics

Substances

  • IGF1 protein, human
  • MAFG protein, human
  • MafG Transcription Factor
  • MicroRNAs
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • RNA, Long Noncoding
  • Repressor Proteins
  • Insulin-Like Growth Factor I