Yin Yang 1 regulates ITGAV and ITGB1, contributing to improved prognosis of colorectal cancer.

ABSTRACT

Yin Yang 1 (YY1) is a multifunctional transcription factor with critical roles in carcinogenesis and metastasis. However, its biological role and clinical impact in colorectal cancer (CRC) remain unclear. In the present study, the function and underlying molecular mechanisms of YY1 in CRC progression were investigated. The immunohistochemistry (IHC) of 143 CRC tissues revealed a significant correlation of low YY1 expression with aggressive clinicopathological features, increased metastasis and recurrence and poor patient survival. Multivariate analysis identified low YY1 expression as an independent poor prognostic factor. Subsequently, the IHC of 66 paired CRC primary tumor and liver metastasis tissues revealed that low YY1 expression in the primary CRC was significantly associated with multiple liver metastases, major hepatectomy, extrahepatic metastasis and poor prognosis. In vitro experiments revealed that YY1 knockdown promoted the migration and invasion of CRC cells. To examine the downstream genes of YY1, a cDNA microarray assay was conducted and the differentially expressed genes between the YY1­knockdown and control cells were compared. Integrin alpha V (ITGAV) and integrin beta 1 (ITGB1) were identified as upregulated hub genes using gene enrichment analysis and protein­protein interaction analyses. Western blotting and IHC confirmed YY1 expression to be negatively correlated with ITGAV and ITGB1 expression. In summary, it was revealed that YY1, as a tumor­suppressor in CRC, contributes to the survival of patients with CRC. Low YY1 expression was associated with the poor prognosis of the patients with primary CRC and liver metastases. YY1 suppressed the expression of ITGAV and ITGB1, and this transcriptional regulation may lead to the suppression of CRC cell migration and invasion.