Department of Biochemistry, Postgraduate of Institute of Medical Education and Research, Chandigarh, India.
Department of Neurosurgery, Postgraduate of Institute of Medical Education and Research, Chandigarh, India.
Gene. 2018 Oct 20;674:31-36. doi: 10.1016/j.gene.2018.06.063. Epub 2018 Jun 23.
The regulation of histone 3 lysine 4 (H3K4) methylation code is indispensable for the cell as any disturbance in this has been associated with many pathologic conditions, like cancer. The SET domain-containing lysine methyltransferase 2 (KMT2) family of histone methyltransferases was the first to be identified as writers of H3K4 methylation. In mammals, seven members of the KMT2 family are responsible for carrying out the bulk of H3K4 methylation. Recent studies documented alterations in various histone methylases in human cancer, which were associated with therapeutic and prognostic potential. Notwithstanding, no report has documented the role of KMT2 family of histone methyltransferases in clear cell renal cell carcinoma (ccRCC). Therefore, we examined the expression profile of all the seven KMT2 family members of histone methyltransferases in ccRCC with the aim to establish their role as prognostic or therapeutic targets. Real-time PCR was employed to study the expression of KMT2 family genes using specific primers in 50 cases of ccRCC. The mRNA levels were correlated with stage, grade, and metastasis of the tumor. Among seven genes, KMT2G was significantly up-regulated in higher stages of the tumor as compared to low stage tumors (p = 0.017). Similarly, KMT2G levels were higher in the metastatic tumor (p = 0.027). Additionally, some of the KMT2G target genes were found to be up-regulated in metastatic tumors as compared to non-metastatic. ROC curve indicated KMT2G as a good marker for discriminating metastatic tumors from non-metastatic tumors (AUC = 0.738). Thus, we conclude that KMT2G histone methyltransferase could be a good prognostic marker for ccRCC. Additionally, KMT2G can also serve as a therapeutic target for ccRCC.
组蛋白 3 赖氨酸 4（H3K4）甲基化密码的调节对于细胞是必不可少的，因为任何对此的干扰都与许多病理状况有关，如癌症。SET 结构域包含的赖氨酸甲基转移酶 2（KMT2）家族的组蛋白甲基转移酶是第一个被确定为 H3K4 甲基化书写者的家族。在哺乳动物中，KMT2 家族的七个成员负责进行大部分 H3K4 甲基化。最近的研究记录了人类癌症中各种组蛋白甲基转移酶的改变，这些改变与治疗和预后潜力有关。然而，没有报道记录 KMT2 家族的组蛋白甲基转移酶在透明细胞肾细胞癌（ccRCC）中的作用。因此，我们检查了所有七个 KMT2 家族的组蛋白甲基转移酶在 ccRCC 中的表达谱，目的是确定它们作为预后或治疗靶点的作用。使用特定引物，通过实时 PCR 研究了 50 例 ccRCC 中 KMT2 家族基因的表达。将 mRNA 水平与肿瘤的分期、分级和转移相关联。在七个基因中，与低分期肿瘤相比，KMT2G 在肿瘤的较高分期中显著上调（p=0.017）。同样，在转移性肿瘤中 KMT2G 水平更高（p=0.027）。此外，与非转移性肿瘤相比，一些 KMT2G 靶基因在转移性肿瘤中上调。ROC 曲线表明 KMT2G 是区分转移性肿瘤和非转移性肿瘤的良好标志物（AUC=0.738）。因此，我们得出结论，KMT2G 组蛋白甲基转移酶可能是 ccRCC 的一个良好预后标志物。此外，KMT2G 也可以作为 ccRCC 的治疗靶点。
