Institute of Molecular Biology, Southern Medical University, Guangzhou 510515, PR China.
Oncol Rep. 2010 Sep;24(3):715-20. doi: 10.3892/or_00000912.
The F-box protein family member FBXO31 has rarely been studied in human hepatocellular carcinoma (HCC). This study was designed to investigate the expression profile of FBXO31 in HCC and the possibility that FBXO31 might function as a tumor suppressor in HCC cell lines. We report that FBXO31 is strongly down-regulated in HCC cell lines and specimens. Ectopic expression of FBXO31 inhibited cell proliferation and colony formation in HepG2 and Hep3B cells. The endogenous expression of FBXO31 was fluctuated through cell cycle in the HepG2 cells with maximal expression from late G2 to early G1 phase. Ectopic expression of FBXO31 in HepG2 resulted in the accumulation of cells at the G1 phase of the cell cycle. Possible mechanism might be cyclin D1 degradation mediate by FBXO31 through ubiquitin ligase pathway. Ectopic overexpression of FBXO31 resulted in down-regulation of cyclin D1 which leads to the accumulation of cells at the G1 phase of the cell cycle. Cytoplasmic location of FBXO31 was consistent with cyclin D1 degradation in cytoplasm. Together, our findings suggested that down-regulation of FBXO31 might function as a tumor suppressor in HCC.
F -box 蛋白家族成员 FBXO31 在人类肝细胞癌 (HCC) 中很少被研究。本研究旨在探讨 FBXO31 在 HCC 中的表达谱，以及 FBXO31 可能作为 HCC 细胞系中的肿瘤抑制因子的可能性。我们报告称，FBXO31 在 HCC 细胞系和标本中强烈下调。FBXO31 的异位表达抑制了 HepG2 和 Hep3B 细胞的增殖和集落形成。在 HepG2 细胞中，内源性 FBXO31 的表达通过细胞周期波动，在 G2 期晚期至 G1 期早期表达达到最大值。FBXO31 的异位表达导致 HepG2 细胞周期 G1 期细胞的积累。可能的机制可能是 FBXO31 通过泛素连接酶途径介导细胞周期蛋白 D1 的降解。FBXO31 的异位过表达导致细胞周期蛋白 D1 的下调，从而导致细胞在 G1 期积累。细胞质中 FBXO31 的定位与细胞质中细胞周期蛋白 D1 的降解一致。总之，我们的研究结果表明，FBXO31 的下调可能在 HCC 中作为肿瘤抑制因子发挥作用。
