The Six Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
The Six Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
Life Sci. 2019 Oct 1;234:116788. doi: 10.1016/j.lfs.2019.116788. Epub 2019 Aug 22.
Livin is an important member of the human inhibitor of apoptosis proteins (IAPs) family. IAPs are proteins with antiapoptotic abilities, and their functions are different from the Bcl-2 (B-cell lymphoma-2) family proteins. However, the precise role of Livin in colon cancer progression remains unclear. The purpose of this study is to assess the effect of overexpression Livin in colon cancer cells and to examine its molecular mechanism. We demonstrated that Livin induced a colon cancer phenotype, including proliferation and migration, by regulating H2A.X (histone family 2A variant (H2AX) phosphorylated on the 39th serine site). We elucidated that Livin degraded Jumonji-C domain-containing 6 protein (JMJD6), which was mediated by the proteasome murine double minute 2 (MDM2), thereby regulating H2A.X. Above all, the overexpression of JMJD6 recovered H2A.X in colon cancer cells with a high level of Livin, thus inhibiting colon cancer malignancy progression. These results reveal a previously unrecognized role for Livin in regulating the tumor-initiating capacity in colon cancer and provide a novel treatment strategy in cancer via the interruption of H2A.X function and the interaction between H2A.X and JMJD6.
Livin 是人类凋亡抑制蛋白（IAPs）家族的重要成员。IAPs 是具有抗凋亡能力的蛋白质，其功能与 Bcl-2（B 细胞淋巴瘤-2）家族蛋白不同。然而，Livin 在结肠癌进展中的确切作用尚不清楚。本研究旨在评估 Livin 在结肠癌细胞中的过表达效应，并研究其分子机制。我们证明 Livin 通过调节 H2A.X（第 39 位丝氨酸位点磷酸化的组蛋白家族 2A 变体（H2AX））诱导结肠癌表型，包括增殖和迁移。我们阐明 Livin 降解了包含 Jumonji-C 结构域的 6 蛋白（JMJD6），这是由蛋白酶体鼠双微体 2（MDM2）介导的，从而调节 H2A.X。最重要的是，JMJD6 的过表达恢复了 Livin 高水平的结肠癌细胞中的 H2A.X，从而抑制了结肠癌的恶性进展。这些结果揭示了 Livin 在调节结肠癌起始能力方面的先前未被认识的作用，并通过中断 H2A.X 功能和 H2A.X 与 JMJD6 之间的相互作用提供了一种新的癌症治疗策略。
