Laboratorio de Biología Molecular, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México.
Posgrado en Ciencias Químicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, México.
FEBS Open Bio. 2020 Nov;10(11):2305-2315. doi: 10.1002/2211-5463.12973. Epub 2020 Sep 24.
Galectin-9 levels have been reported to be altered in several cancer types, but the mechanism that regulates the expression of Galectin-9 has not been clarified. Galectin-9 is encoded by the LGALS9 gene, which gives rise to eight mRNA variants. The aims of this study were: (a) to identify the mRNA variants of LGALS9, (b) to characterize CpG methylation and H3K9 and H3K14 histone acetylation at the promoter of the LGALS9 gene, and (c) to characterize the relationship between these modifications and LGALS9 expression level in cervical cancer cells. All mRNA variants were detected in HaCaT (nontumoural keratinocytes) and SiHa cells, and seven were observed in HeLa cells. The promoter region of LGALS9 contains eight CpG dinucleotides. No hypermethylation pattern related to low LGALS9 expression was identified in tumour cells. Chromatin immunoprecipitation analysis demonstrated higher acetylation of H3K9ac and H3K14ac in HaCaT cells, which was related to higher mRNA levels. The presence of the mRNA variants suggests that alternative splicing may regulate the expression of galectin-9 isoforms. The results of this study suggest that histone acetylation, but not promoter CpG methylation, may be involved in the transcriptional regulation of the LGALS9 gene.
半乳糖凝集素-9（Galectin-9）水平在几种癌症类型中被报道发生改变，但调节 Galectin-9 表达的机制尚未阐明。Galectin-9 由 LGALS9 基因编码，该基因产生 8 种 mRNA 变体。本研究的目的是：（a）鉴定 LGALS9 的 mRNA 变体，（b）描述 LGALS9 基因启动子处的 CpG 甲基化以及 H3K9 和 H3K14 组蛋白乙酰化，（c）描述这些修饰与宫颈癌细胞中 LGALS9 表达水平之间的关系。所有 mRNA 变体均在 HaCaT（非肿瘤角质形成细胞）和 SiHa 细胞中检测到，在 HeLa 细胞中观察到 7 种变体。LGALS9 的启动子区域含有 8 个 CpG 二核苷酸。在肿瘤细胞中未发现与 LGALS9 低表达相关的高甲基化模式。染色质免疫沉淀分析表明，HaCaT 细胞中 H3K9ac 和 H3K14ac 的乙酰化水平更高，这与更高的 mRNA 水平相关。mRNA 变体的存在表明，选择性剪接可能调节半乳糖凝集素-9 同工型的表达。本研究结果表明，组蛋白乙酰化而不是启动子 CpG 甲基化可能参与 LGALS9 基因的转录调控。
