MiR-20b, -21, and -130b inhibit PTEN expression resulting in B7-H1 over-expression in advanced colorectal cancer

Abstract

Co-inhibitor B7-H1 expresses in various cancers and contributes to cancer immune evasion by inhibiting T cell activation and proliferation, yet the regulatory mechanisms for B7-H1 over-expression in cancers remain largely unknown. Here, the expression of B7-H1 and PTEN proteins were firstly detected by using immunohistochemistry method. B7-H1 immunoreactivities were found in 54.5% (55/101) of the colorectal cancer tissues with no expression in the normal tissues, and the PTEN protein immunoreactivities were observed in 51.5% (52/101) of the colorectal cancer tissues and 72.3% (73/101) of the normal tissues. Statistical analysis results indicated that the B7-H1 expression was negatively correlated to the PTEN expression in colorectal cancer (p=0.001). Then the expressions of microRNAs (miRNAs) in six pairs of colorectal cancer and normal tissues were determined by miRNA array, and 30 up-regulated miRNAs were found in the colorectal cancer tissues. Finally, the impact of these up-regulated miRNAs on PTEN expression was tested by using dual-luciferase reporter assay system, from which the results indicated that miR-20b, -21, and -130b were involved in suppression of PTEN expression. These findings suggest that miR-20b, -21, and -130b, up-regulated in colorectal cancer, through inhibiting the expression of PTEN, result in B7-H1 over-expression in colorectal cancer.