CRTAC1 (Cartilage acidic protein 1) inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in bladder cancer by downregulating Yin Yang 1 (YY1) to inactivate the TGF-β pathway

Abstract

Cartilage acidic protein 1 (CRTAC1) is predicted to be aberrantly expressed in bladder cancer based on bioinformatics analysis. However, its functions and molecular mechanism in bladder cancer remain elusive. This study aimed to explore the role of CRTAC1 in bladder cancer. The mRNA and protein levels of CRTAC1 and Yin Yang 1 (YY1) were detected by reverse transcription quantitative polymerase chain reaction and western blotting. We found that CRTAC1 was downregulated in bladder cancer tissues and cells. Cell Counting Kit-8 assays, colony formation assays, wound healing assays and Transwell assays and western blotting revealed that CRTAC1 overexpression inhibited cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in bladder cancer, while CRTAC1 knockdown exerted opposite effects on these malignant behaviors. Mechanistically, CRTAC1 targeted YY1 in bladder cancer cells. YY1 was upregulated in bladder cancer tissues and cells. CRTAC1 negatively modulated the mRNA and protein expression of YY1 in bladder cancer cells. Co-localization of CRTAC1 and YY1 expression was assessed using immunofluorescence staining and Co-Immunoprecipitation assays. The interaction between CRTAC1 and YY1 was explored by Chromatin immunoprecipitation and luciferase reporter assays. Moreover, CRTAC1 inactivated the TGF-β pathway by downregulating YY1 expression. Protein levels of factors associated with the TGF-β pathway were examined by western blotting. Rescue assays indicated that CRTAC1 inhibited malignant behaviors of bladder cancer cells by targeting YY1. Overall, CRTAC1 inhibited malignant phenotypes of bladder cancer cells by targeting YY1 to inactivate the TGF-β pathway.

The origin of bladder cancer from mucosal field effects

“…Their downregulation in association with field effects signifies the aberrant differentiation program in bladder mucosa setting up the organ for basal cancer development. We also observed downregulation of MUC15 and CRTAC1 , both of which encode extracellular glycoprotein complexes but their role in urothelial biology is uncertain ( Steck et al., 2007 ; Yang et al., 2021 ; Yue et al., 2020 ; Zhang et al., 2020b ).…”

Determination of WWOX Function in Modulating Cellular Pathways Activated by AP-2α and AP-2γ Transcription Factors in Bladder Cancer

“…Thus, it was decided to search for an appropriate target of this transcription factor to certify its anti-cancer characteristics specifically in BLCA. It turned out that CRTAC1 is of interest for bladder cancer since it inhibits many pro-tumorigenic processes including cell viability and migration [67]. To recapitulate, the decrease in both IL1A and MAP3K7 (during AP-2α overexpression) or only MAP3K7 (during WWOX overexpression) can further lead to an increase in TCF7L1, which affects metastasis and CRTAC1 expression.…”

A Multi-Omics Study on the Effect of Helicobacter Pylori-Related Genes in the Tumor Immunity on Stomach Adenocarcinoma

“…The three candidate genes detected in this study were CRTAC1 , BATF2 , and CTHRC1 . Evidence shows that cartilage acidic protein 1 (CRTAC1) is related to various malignancies, including bladder cancer and lung adenocarcinoma, by inhibiting the cell proliferation, migration, invasion, and epithelial–mesenchymal transition processes ( Yang et al., 2021 ; Yu et al., 2021 ). However, the role of CRTAC1 has not yet been reported in STAD or other gastric cancer.…”