LncRNA HOXB-AS3 binding to PTBP1 protein regulates lipid metabolism by targeting SREBP1 in endometrioid carcinoma

Life Sci. 2023 May 1:320:121512. doi: 10.1016/j.lfs.2023.121512. Epub 2023 Feb 27.

Abstract

Endometrial cancer (EC) is a malignant tumor with a high incidence in women, and the survival rate of high-risk patients decreases significantly after disease progression. The regulatory role of long non-coding RNAs (LncRNAs) in tumors has been widely appreciated, but there have been few studies in EC. To investigate the effect of HOXB-AS3 in EC, we used bioinformatics tools for prediction and collected clinical samples to detect the expression of HOXB-AS3. Colony formation assay, MTT assay, flow cytometry and apoptosis assay, and transwell assay were used to verify the role of HOXB-AS3 in EC. HOXB-AS3 was upregulated in EC, promoted the proliferation and invasive ability of EC cells, and inhibited apoptosis. In addition, the ROC curve illustrated its diagnostic value. We explored experiments via lentiviral transduction, FISH, Oil Red O staining, TC and FFA content detection, RNA-pulldown, RIP, and other mechanisms to reveal that HOXB-AS3 can bind to PTBP1 and co-regulate the expression of SREBP1, thereby regulating lipid metabolism in EC cells. To the best of our knowledge, this is the first study on HOXB-AS3 in disorders of lipid metabolism in EC. In addition, we believe HOXB-AS3 has the potential to be a neoplastic marker or a therapeutic target.

Keywords: Endometrioid endometrial cancer; HOXB-AS3; PTBP1; SREBP1.

MeSH terms

  • Carcinoma, Endometrioid* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Endometrial Neoplasms* / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • Lipid Metabolism
  • MicroRNAs* / genetics
  • Polypyrimidine Tract-Binding Protein / genetics
  • Polypyrimidine Tract-Binding Protein / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sterol Regulatory Element Binding Protein 1 / metabolism

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • MicroRNAs
  • Polypyrimidine Tract-Binding Protein
  • PTBP1 protein, human
  • RNA, Long Noncoding
  • Sterol Regulatory Element Binding Protein 1