LINC00470 promotes malignant progression of testicular germ cell tumors

Mol Biol Rep. 2024 Nov 14;51(1):1152. doi: 10.1007/s11033-024-10083-w.

Abstract

Background: Testicular germ cell tumor (TGCT) is a common malignant tumor in adolescents. Now, many long non-coding RNAs (LncRNAs) have been found to have an important function in TGCT. LINC00470 is specifically and highly expressed in TGCT, however, there is still no definite information concerning its role and underlying mechanism in TGCT. The purpose of this research was to look into the involvement of LINC00470 in TGCT and its intrinsic mechanism.

Methods and results: UCSC and GEPIA2 databases were used to analyze the expression of LINC00470, and the BEST website was used to perform GSEA enrichment analysis, immune infiltration analysis, and drug susceptibility analysis. SiRNA transfection was used to silence LINC00470 in TCAM-2 and NCCIT cells. Clone formation and Transwell assays were performed in TGCT cells to confirm the effects of LINC00470 on clone formation, migration, and invasion. Western Blot was performed to determine the expression of proteins related to the EMT and AKT signaling pathways. LINC00470 was specifically highly expressed in TGCT, and played a role in promoting tumor cell clone formation and cell metastasis by affecting the TGF-β and PI3K-AKT-mTOR signaling pathways to regulate the epithelial-mesenchymal transition (EMT) process; LINC00470 may also play a pro-tumor role by negatively regulating immune infiltration; in addition, the expression of LINC00470 was negatively correlated with the chemosensitivity of cisplatin in TGCT patients.

Conclusions: LINC00470 may play a significant role in the etiology and metastasis of TGCT through EMT and AKT-mediated signaling pathways.

Keywords: AKT; Cell metastasis; Epithelial-mesenchymal transition; Immune response; LINC00470; Testicular germ cell tumor.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal* / genetics
  • Neoplasms, Germ Cell and Embryonal* / metabolism
  • Neoplasms, Germ Cell and Embryonal* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction* / genetics
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Testicular Neoplasms* / genetics
  • Testicular Neoplasms* / metabolism
  • Testicular Neoplasms* / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Phosphatidylinositol 3-Kinases
  • Transforming Growth Factor beta

Supplementary concepts

  • Testicular Germ Cell Tumor