TAGLN2 Promotes the Proliferation, Migration, Invasion, and EMT of Clear Cell Renal Cell Carcinoma Through the PI3K/Akt Signaling Pathway

Biochem Genet. 2023 Aug;61(4):1265-1281. doi: 10.1007/s10528-022-10319-z. Epub 2022 Dec 22.

Abstract

The effect of Transgelin 2 (TAGLN2) on clear cell renal cell carcinoma (ccRCC) is unknown. This study explored the potential role and mechanism of ccRCC. The expression of TAGLN2 in Pan-cancers was analyzed using the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. TCGA-KIRC database was used to analyze subsequent prognostic survival, pathway enrichment, and immune infiltration. Relevant experimental methods could explain the effect of TAGLN2 expression on tumor cell proliferation, migration, invasion, and apoptosis. Apoptosis, proliferation, Epithelial-to-Mesenchymal Transition (EMT), and PI3K/AKT signaling pathway-related protein expression were determined through western blotting. In the TCGA + GTEx database, mRNA-TAGLN2 expression was clearly increased in pan-cancer tissues, and the same result was found in ccRCC patients based on KIRC analysis results. In addition, TAGLN2 was associated with poor clinical stage, pathological grade, and survival prognosis. TAGLN2 is highly expressed in ccRCC tissues and in vitro TAGLN2 silencing of cells inhibits the proliferation, migration, invasion, and EMT of ccRCC cancer cells. Furthermore, TAGLN2-related differential genes enriched in the PI3K/AKT signaling pathway were negatively regulated after TAGLN2 silencing. Moreover, TAGLN2 may promote tumor immune escape and increase the risk of distant metastasis in immune infiltration-related analyses. TAGLN2 can be used as a single indicator to explain the survival probability of patients with ccRCC. In vitro TAGLN2 silencing inhibited the malignant properties of ccRCC by blocking the PI3K/AKT signaling pathway. In addition, TAGLN2 contributes to tumor immune escape and may be a potential therapeutic target for ccRCC.

Keywords: AKT; EMT; Immune infiltration; PI3K; TAGLN2; ccRCC.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / metabolism
  • Carcinoma, Renal Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Kidney Neoplasms* / genetics
  • Kidney Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases