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.
Bcl2l10 mediates the proliferation, invasion and migration of ovarian cancer cells
INTERNATIONAL JOURNAL OF ONCOLOGY
Authors: Lee, Su-Yeon; Kwon, Jinie; Woo, Ji Hye; Kim, Kyeoung-Hwa; Lee, Kyung-Ah
Abstract
Bcl2l10, also known as Diva, Bcl-b and Boo, is a member of the Bcl2 family of proteins, which are involved in signaling pathways that regulate cell apoptosis and autophagy. Previously, it was demonstrated that Bcl2l10 plays a crucial role in the completion of oocyte meiosis and is a key regulator of Aurora kinase A (Aurka) expression and activity in oocytes. Aurka is overexpressed in several types of solid tumors and has been considered a target of cancer therapy. Based on these previous results, in the present study, the authors aimed to investigate the regulatory role of Bcl2l10 in A2780 and SKOV3 human ovarian cancer cells. The protein expression of Bcl2l10 was examined in human cancer tissues and cell lines, including the ovaries, using a tissue microarray and various human ovarian cancer cell lines. It was found that Bcl2l10 regulated the protein stability and activities of Aurka in ovarian cancer cells. Although apoptosis was not affected, the cell cycle was arrested at the G0/G1 phase by Bcl2l10 knockdown. Of note, cell viability and motility were markedly increased by Bcl2l10 knockdown. On the whole, the findings of this study suggest that Bcl2l10 functions as tumor suppressor gene in ovarian cancer.