title: Primary microcephaly gene MCPH1 shows a novel molecular biomarker of human renal carcinoma and is regulated by miR-27a.
abstract: 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.
authors.affiliation: Department of Pathology, Shaoxing Hospital of Traditional Chinese Medicine Shaoxing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pathology, Taizhou Hospital of Taizhou Enze Medical Group Linhai, China.
authors.forename: Weifei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pathology, Taizhou Hospital of Taizhou Enze Medical Group Linhai, China.
authors.forename: Meifu
authors.initials: M
authors.lastname: Gan
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Xuequan
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Pathology, Shaoxing Hospital of Traditional Chinese Medicine Shaoxing, China.
authors.forename: Jushi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Taizhou Central Hospital of Taizhou Enze Medical Group Taizhou, China.
authors.forename: Lanxi
authors.initials: L
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D018797:Cell Cycle Proteins; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins
keywords: MCPH1; Renal carcinoma; miR-27; microRNA; suppressor gene