The lncRNA TPTEP1 suppresses PI3K/AKT signalling and inhibits ovarian cancer progression by interacting with PTBP1

J Cell Mol Med. 2024 Oct;28(20):e70106. doi: 10.1111/jcmm.70106.

Abstract

The expression of the long noncoding RNA (lncRNA) TPTE pseudogene 1 (TPTEP1) is significantly downregulated in ovarian cancer (OC). However, the function and mechanism of the lncRNA TPTEP1 in OC have not been identified. To investigate the expression of the lncRNA TPTEP1, we analysed a publicly available dataset and 20 pairs of OC and normal ovarian samples tissue from the First Affiliated Hospital of Anhui Medical University. Functional assays were used to determine the role of the lncRNA TPTEP1 in OC progression. Furthermore, Western blot, FISH, RNA pull-down, mass spectrometry and RNA immunoprecipitation approaches were used to determine the mechanism by which the lncRNA TPTEP1 affects OC progression. Animal experiments were used to determine the role of the lncRNA TPTEP1 in ovarian tumorigenicity in vivo. The expression of the lncRNA TPTEP1 in OC tissues was significantly lower than that in normal tissues and low expression of the lncRNA TPTEP1 was significantly correlated with advanced FIGO stage and the presence of malignant ascites in OC patients. In vitro and in vivo, regulation of the expression of the lncRNA TPTEP1 caused changes in OC cell proliferation, migration, invasion and apoptosis. Mechanistically, we found that TPTEP1 directly binds to the polypyrimidine tract-binding protein 1 (PTBP1) protein and inhibits PI3K/AKT signalling. The lncRNA TPTEP1 inhibits PI3K/AKT signalling by directly binding PTBP1, possibly indicating the molecular mechanism underlying its biological function. With further research, these findings may aid in the development of clinically useful strategies for the treatment of OC.

Keywords: PI3K/AKT; PTBP1; lncRNA; ovarian cancer.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Heterogeneous-Nuclear Ribonucleoproteins* / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins* / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Middle Aged
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Polypyrimidine Tract-Binding Protein* / genetics
  • Polypyrimidine Tract-Binding Protein* / metabolism
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction*

Substances

  • RNA, Long Noncoding
  • Polypyrimidine Tract-Binding Protein
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • PTBP1 protein, human