LTB4R Promotes the Occurrence and Progression of Clear Cell Renal Cell Carcinoma (ccRCC) by Regulating the AKT/mTOR Signaling Pathway

Cells. 2022 Nov 15;11(22):3606. doi: 10.3390/cells11223606.

Abstract

ccRCC is highly immunogenic, yet its underlying immune-related molecular mechanisms are unknown. Leukotriene B4 Receptor 1 (LTB4R), a novel immune-related gene associated in our previous research with the prognosis of ccRCC patients, has been found in many cancers; however, its potential mechanism in renal clear carcinoma is unclear. This study was conducted to investigate LTB4R's action mechanism in renal clear cell carcinoma. First, a CCK8 assay was performed to verify LTB4R's effect on the proliferation viability of renal clear cell carcinoma cells. Scratch and transwell assays verified LTB4R's effect on the migration and invasion ability of renal clear cell carcinoma cells. Flow cytometry validated LTB4R's effect on renal clear cell carcinoma cells' apoptosis and cell cycle. A Western blot assay was conducted to further investigate LTB4R's effect on apoptosis, cell cycle, EMT process, and AKT/mTOR signaling pathway in renal clear cell carcinoma at the protein level. In vitro experiments showed that LTB4R knockdown inhibited the proliferation, migration, and invasion of renal clear cell carcinoma cells and promoted their apoptosis, whereas LTB4R overexpression promoted the proliferation, migration, and invasion of renal clear cell carcinoma cells and inhibited their apoptosis. In addition, we found that LTB4R regulated the proliferation and apoptosis of renal clear cell carcinoma cells by regulating the AKT/mTOR signaling pathway's phosphorylation process. Furthermore, we verified some of these results using bioinformatic analysis. LTB4R plays an oncogenic role in renal clear cell carcinoma; it is expected to be a molecular target for renal clear cell carcinoma treatment and a predictive biomarker for prognosis.

Keywords: AKT/mTOR signaling pathway; LTB4R; apoptosis; cell cycle; clear cell renal cell carcinoma.

MeSH terms

  • Carcinoma, Renal Cell* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Leukotriene B4 / genetics
  • Receptors, Leukotriene B4 / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Receptors, Leukotriene B4
  • TOR Serine-Threonine Kinases
  • MTOR protein, human
  • LTB4R protein, human

Grants and funding

This research received no external funding.