Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
Environmental Health Center for Childhood Leukaemia and Cancer, Department of Pediatrics, Chonnam National University Hwasun Hospital, Hwasun 519-809, Republic of Korea.
Sci Rep. 2017 Apr 7;7:46182. doi: 10.1038/srep46182.
Recent studies have reported the ectopic expression of olfactory receptors (ORs) in non-olfactory tissues, however, their physiological roles were not well elucidated. ORs are expressed in and function in different types of cancers. Here, we identified that the H3K9me2 levels of several OR promoters decreased during differentiation in the HL-60, human myeloid leukaemia cell line, by all-trans-retinoic acid (ATRA). We found that the differential OR promoters H3K9me2 levels were regulated by G9a and LSD1, resulting in the decrease of ORs transcription during HL-60 differentiation. G9a and LSD1 could regulate the expression of ORs in several non-olfactory cells via the methylation and demethylation of H3K9me2. In addition, we demonstrated that knockdown of OR significantly reduced cell proliferation. Therefore, the epigenetic regulation of ORs transcription is critical for carcinogenesis.
最近的研究报道了嗅觉受体（ORs）在非嗅觉组织中的异位表达，但其生理作用尚未得到很好的阐明。ORs 在不同类型的癌症中表达并发挥作用。在这里，我们发现全反式维甲酸（ATRA）诱导 HL-60 人髓样白血病细胞系分化过程中，几个 OR 启动子的 H3K9me2 水平降低。我们发现，不同的 OR 启动子 H3K9me2 水平受到 G9a 和 LSD1 的调节，导致 HL-60 分化过程中 ORs 转录减少。G9a 和 LSD1 可以通过 H3K9me2 的甲基化和去甲基化调节几种非嗅觉细胞中 ORs 的表达。此外，我们证明 OR 的敲低显著降低了细胞增殖。因此，ORs 转录的表观遗传调控对致癌作用至关重要。
