Variations in the AURKA Gene: Biomarkers for the Development and Progression of Hepatocellular Carcinoma
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Authors: Wang, Bin; Hsu, Chin-Jung; Chou, Chia-Hsuan; Lee, Hsiang-Lin; Chiang, Whei-Ling; Su, Chen-Ming; Tsai, Hsiao-Chi; Yang, Shun-Fa; Tang, Chih-Hsin
Abstract
Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. AURKA (aurora kinase A) is a mitotic serine/threonine kinase that functions as an oncogene and plays a critical role in hepatocarcinogenesis. We report on the association between 4 single nucleotide polymorphisms (SNPs) of the AURKA gene (rs1047972, rs2273535, rs2064836, and rs6024836) and HCC susceptibility as well as clinical outcomes in 312 patients with HCC and in 624 cancer-free controls. We found that carriers of the TT allele of the variant rs1047972 were at greater risk of HCC compared with wild-type (CC) carriers. Moreover, carriers of at least one A allele in rs2273535 were less likely to progress to stage III/IV disease, develop large tumors or be classified into Child-Pugh class B or C. Individuals with at least one G allele at AURKA SNP rs2064863 were at lower risk of developing large tumors or progressing to Child-Pugh grade B or C. Our results indicate that genetic variations in the AURKA gene may serve as an important predictor of early-stage HCC and be a reliable biomarker for the development of HCC.
Wwc2Is a Novel Cell Division Regulator During Preimplantation Mouse Embryo Lineage Formation and Oogenesis
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Authors: Virnicchi, Giorgio; Bora, Pablo; Gahurova, Lenka; Susor, Andrej; Bruce, Alexander W.
Abstract
Formation of the hatching mouse blastocyst marks the end of preimplantation development, whereby previous cell cleavages culminate in the formation of three distinct cell lineages (trophectoderm, primitive endoderm and epiblast). We report that dysregulated expression ofWwc2, a genetic paralog ofKibra/Wwc1(a known activator of Hippo-signaling, a key pathway during preimplantation development), is specifically associated with cell autonomous deficits in embryo cell number and cell division abnormalities. Division phenotypes are also observed during mouse oocyte meiotic maturation, asWwc2dysregulation blocks progression to the stage of meiosis II metaphase (MII) arrest and is associated with spindle defects and failed Aurora-A kinase (AURKA) activation. Oocyte and embryo cell division defects, each occurring in the absence of centrosomes, are fully reversible by expression of recombinant HA-epitope tagged WWC2, restoring activated oocyte AURKA levels. Additionally, clonal embryonic dysregulation implicatesWwc2in maintaining the pluripotent epiblast lineage. Thus,Wwc2is a novel regulator of meiotic and early mitotic cell divisions, and mouse blastocyst cell fate.