Histone methyltransferase KMT5A gene modulates oncogenesis and lipid metabolism of papillary thyroid cancer in vitro
Histone methyltransferase KMT5A gene modulates oncogenesis and lipid metabolism of papillary thyroid cancer in vitro
复制标题
组蛋白甲基转移酶KMT5A基因体外调节甲状腺乳头状癌的肿瘤发生和脂质代谢
DOI：
10.3892/or.2018.6295
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发表时间：
2018-05-01
期刊：
影响因子：
4.2
通讯作者：
Ji, Qing-Hai
中科院分区：
文献类型：
--
作者：
Liao, Tian;Wang, Yuan-Jin;Ji, Qing-Hai
KMT 5A（称为PR-Set 7/9、SETD 8和SET 8）是特异性靶向H4 K20甲基化的含有SET结构域的甲基转移酶家族的成员，已经涉及多种生物学过程。在本研究中，我们确定，KMT 5A升高，在50对甲状腺乳头状癌组织样本和细胞系K1和TPC-1的qRT-PCR和蛋白质印迹，以及免疫组化染色。CCK-8法和流式细胞术分析显示，抑制KMT 5A可抑制细胞增殖，诱导细胞凋亡。Transwell实验显示，KMT 5A基因敲除的细胞迁移和侵袭受到抑制。抑制KMT 5A可使甲状腺乳头状癌细胞周期阻滞于G1/S期。TCGA结果显示KMT 5A的高表达与甲状腺外浸润、淋巴结转移及病理分期密切相关。此外，我们观察到KMT 5A的抑制抑制了SREBP 1，SCD，FREB和ACC，参与脂质代谢的关键分子的表达，并降低了甲状腺乳头状癌细胞中丙二醛的水平。总之，KMT 5A可能是一种新的致癌因子，特别是在甲状腺乳头状癌的脂质代谢调节。
KMT5A (known as PR-Set7/9, SETD8 and SET8), a member of the SET domain containing methyltransferase family specifically targeting H4K20 for methylation, has been implicated in multiple biological processes. In the present study, we identified that KMT5A was elevated in 50 pairs of papillary thyroid cancer tissue samples and in cell lines K1 and TPC-1 by qRT-PCR and western blotting, as well as by immunohistochemical staining. CCK-8 assay and flow cytometric analysis revealed that inhibition of KMT5A attenuated proliferation and induced apoptosis. Transwell assays revealed that cell migration and invasion were suppressed in KMT5A-knockdown cells. Moreover, the inhibition of KMT5A arrested the cell cycle in the G1/S phase of papillary thyroid cancer cells. The TCGA data revealed that elevated KMT5A expression was significantly correlated with extrathyroidal extension, lymph node metastasis and advanced pathological stage of papillary thyroid cancer. Furthermore, we observed that inhibition of KMT5A suppressed the expression of SREBP1, SCD, FASN and ACC, key molecules involved in lipid metabolism and decreased the level of malondialdehyde in papillary thyroid cancer cells. In conclusion, KMT5A may be a novel oncogenic factor, specifically a regulator for lipid metabolism in papillary thyroid carcinoma.