Early stage or localized melanoma can be surgically resected with satisfactory outcome, whereas advanced malignant melanoma responds to treatment poorly and has a negative prognosis even after surgery, radiotherapy and other comprehensive treatments. Gene therapy targeting various biological signaling pathways has become an increasingly popular area in melanoma research. However, for gene therapy success, it is important to reveal the molecular mechanisms of melanoma tumorigenesis and development. The present study examined the effects of downregulating enhancer of rudimentary homolog (ERH) expression on the proliferation, metastasis and cell cycle of melanoma cells. ERH expression levels in melanoma tissues and cells were determined. Then, ERH gene expression in melanoma cell lines was downregulated or overexpressed by the lentiviral RNA interference technique. Furthermore, we performed cell counting kit-8, clone formation, scratch, transwell migration, subcutaneous tumorigenesis and venous metastasis assays as well as carried out flow cytometry analysis to explore the effects of ERH expression on cell proliferation, cell cycle, apoptosis and metastasis. We found that ERH expression in melanoma tissues and cells was markedly higher than in normal melanin nevus. Suppressing ERH expression by RNA interference in melanoma A375, WM35 and SK28 cell lines inhibited their proliferation and induced cell apoptosis. The cell cycle was also found to be blocked in the G1 phase. However, the metastatic properties of melanoma cells in vitro and in vivo remained largely unaltered by ERH knockdown. Our results show that ERH expression is increased in melanoma. Meanwhile, the proliferation and cell cycle transformation abilities are impaired potentially by downregulating the ERH expression in melanoma cells. Therefore, targeting ERH might serve as a novel therapeutic approach for malignant melanoma.

中文翻译：

---

基本同系物表达增强子的敲低会减弱黑色素瘤细胞的增殖、细胞周期和凋亡。


早期或局限性黑色素瘤可以通过手术切除获得满意的疗效，而晚期恶性黑色素瘤治疗效果较差，即使经过手术、放疗等综合治疗，预后也不佳。针对各种生物信号通路的基因治疗已成为黑色素瘤研究中越来越受欢迎的领域。然而，为了基因治疗的成功，揭示黑色素瘤发生和发展的分子机制非常重要。本研究探讨了下调基本同系物增强子（ERH）表达对黑色素瘤细胞增殖、转移和细胞周期的影响。测定黑色素瘤组织和细胞中的ERH表达水平。然后，通过慢病毒RNA干扰技术下调或过表达黑色素瘤细胞系中的ERH基因表达。此外，我们还进行了细胞计数kit-8、克隆形成、划痕、transwell迁移、皮下肿瘤发生和静脉转移实验，并进行流式细胞术分析，探讨ERH表达对细胞增殖、细胞周期、凋亡和转移的影响。我们发现黑色素瘤组织和细胞中ERH的表达明显高于正常黑色素痣。在黑色素瘤 A375、WM35 和 SK28 细胞系中通过 RNA 干扰抑制 ERH 表达，可抑制其增殖并诱导细胞凋亡。还发现细胞周期被阻断在G1期。然而，黑色素瘤细胞在体外和体内的转移特性在很大程度上并未因 ERH 敲低而改变。我们的结果表明，ERH 表达在黑色素瘤中增加。 同时，黑色素瘤细胞中 ERH 表达的下调可能会损害增殖和细胞周期转化能力。因此，靶向ERH可能成为恶性黑色素瘤的一种新的治疗方法。