Lysine-specific demethylase 5C promotes hepatocellular carcinoma cell invasion through inhibition BMP7 expression.
Lysine-specific demethylase 5C promotes hepatocellular carcinoma cell invasion through inhibition BMP7 expression.
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DOI：
10.1186/s12885-015-1798-4
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发表时间：
2015-10-26
期刊：
影响因子：
3.8
通讯作者：
Dong L
中科院分区：
文献类型：
--
作者：
Ji X;Jin S;Qu X;Li K;Wang H;He H;Guo F;Dong L
肝细胞癌（HCC）是最常见的肿瘤类型，并且与高发病率和死亡率相关。HCC患者常规接受手术，然后进行辅助放疗和化疗。尽管有这些积极的治疗方法，在大多数情况下，中位生存时间仍低于1年。KDM 5C是含有JmjC结构域的蛋白质家族的成员，其从组蛋白H3赖氨酸4（H3 K4）上的甲基化赖氨酸4去除甲基残基。KDM 5C已被认为是多种肿瘤的癌基因，然而，其在HCC中的作用和潜在机制仍不清楚。RT-PCR和免疫组化检测KDM 5C的表达水平。逆转录病毒介导KDM 5C的强制表达，表达慢病毒的shRNA下调KDM 5C。分别采用伤口愈合法、Transwell法和Matrigel法检测肝癌细胞的迁移和侵袭能力。在这项研究中，我们报告KDM 5C在侵袭性人肝癌细胞中大量表达。转染KDM 5C的shRNA能抑制肝癌细胞的迁移、侵袭和上皮-间质转化，并显著降低肝癌细胞在肝、肺的转移能力。此外，KDM 5C在HCC细胞中的异位表达通过BMP 7的失活促进细胞迁移、侵袭和上皮-间质转化。BMP 7的敲低显著促进shKDM 5C诱导的细胞迁移抑制。总之，这些数据表明KDM 5C介导的BMP 7失活对于HCC细胞侵袭是必不可少的。本文的在线版本（doi：10.1186/s12885-015-1798-4）包含补充材料，可供授权用户使用。
Hepatocellular carcinoma (HCC) is the most common type of tumor and is associated with high morbidity and mortality rates. Patients with HCC routinely undergo surgery followed by adjuvant radiation therapy and chemotherapy. Despite such aggressive treatment approaches, median survival times remain under 1 year in most cases. KDM5C is a member of the family of JmjC domain-containing proteins that removes methyl residues from methylated lysine 4 on histone H3 lysine 4 (H3K4). KDM5C has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in HCC remain unclear. Expression level of KDM5C was examined by RT-PCR, and IHC. Forced expression of KDM5C was mediated by retroviruses, and KDM5C was downregulated by shRNAs expressing lentiviruses. Migration and invasion of HCC cells was measured by wound healing, Transwell and Matrigel assays respectively. In this study, we report that KDM5C is abundantly expressed in invasive human HCC cells. Cellular depletion of KDM5C by shRNA inhibited HCC cell migration, invasion and epithelial-mesenchymal transition in vitro, and markedly decreased the metastasis capacity of invasive HCC cells in the liver and lung. Furthermore, ectopic expression of KDM5C in HCC cells promoted cell migration, invasion and epithelial-mesenchymal transition via the inactivation of BMP7. Knockdown of BMP7 significantly promotes shKDM5C-induced cell migration inhibition. Taken together, these data suggest that KDM5C-mediated BMP7 inactivation is essential for HCC cell invasion. The online version of this article (doi:10.1186/s12885-015-1798-4) contains supplementary material, which is available to authorized users.