Primary microcephaly gene MCPH1 shows a novel molecular biomarker of human renal carcinoma and is regulated by miR-27a.

Microcephalin 1 (MCPH1) gene, initially identified as an hTERT repressor, result in two autosomal recessive disorders: primary microcephaly and premature chromosome condensation syndrome. Recently, several studies have found that MCPH1 has also been shown to be downregulated in several different types of human cancers, suggesting that it could also function as a tumor suppressor gene and a novel molecular biomarker of human cancers. To investigate its potential role in the human renal carcinoma progression, we evaluated the expression of protein MCPH1 in 188 renal cancer and 20 normal renal tissues from 188 patients with renal cancer and 20 healthy persons by immunohistochemistry. Positive MCPH1 staining was found in all normal renal samples and partly in cancerous tissues. But MCPH1-positive cells resulted significantly lower in renal carcinoma tissues compared with normal tissues. We further observed that overexpression of MCPH1 decreased cellular proliferation, cell migration and invasion and induced cell apoptosis, indicating it is tumor suppressor. Using bioinformatics approaches and luciferase reporter assay, we showed that the 3'-UTR of MCPH1 harbors two non-overlapping functional seed regions for miR-27 which negatively regulated its level. The expression level of miR-27a negatively correlated with the MCPH1 protein level in renal cancer. Our study indicates for the first time that, in addition to its role in brain development, MCPH1 also functions as a tumor suppressor gene and is directly regulated by miR-27a.