Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(16):6997-7007. doi: 10.26355/eurrev_201908_18740.
Metastatic melanoma, which is refractory to therapies, is one of the most aggressive types in skin cancers. microRNAs (miRNAs) have recently emerged as novel molecules which have therapeutic effects on melanoma. This study focused on the roles and mechanisms of miR-200a in melanoma progression.
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of miR-200a expression in 46 pairs of melanoma tissues and para-cancerous specimens, and the relationship between miR-200a level and clinical features of melanoma patient prognosis was analyzed. MiR-200a expression in melanoma cells was further verified by qRT-PCR. In addition, we identified the biological target of miR-200a using TargetScan. To delineate the molecular mechanism underlying the tumor-suppressive roles of miR-200a in melanoma, Western blots were performed to determine the functions of miR-200a in PI3K/Akt pathway and EMT.
QRT-PCR analysis demonstrated a prominent decrease of miR-200a in melanoma tissues, which was associated with the poor prognosis and malignant clinicopathologic features of melanoma patients. Moreover, functional assays indicated that miR-200a overexpression markedly repressed melanoma cell proliferation, invasion, and migration capacities. A luciferase reporter analysis showed that Golgi membrane protein 1 (GOLM1) was a functional target of miR-200a in melanoma cells. Western blot analysis revealed that miR-200a inhibited melanoma progression by regulating PI3K/Akt signaling pathway and epithelial-mesenchymal transition (EMT). It was also found that miR-200a upregulation markedly suppressed melanoma tumorigenesis in vivo. All these data showed that miR-200a served as a promising therapeutic target in melanoma patients.
We provided evidence that miR-200a was down-regulated in melanoma and was implicated in melanoma progression via inhibiting GOLM1 expressions and regulating PI3K/Akt signaling pathway and EMT. Decreased levels of miR-200a were related to poor prognosis of melanoma patients. Findings of the present study provided a novel insight into understanding melanoma pathogenesis, suggesting that miR-200a may function as a promising and potential therapeutic biomarker for melanoma treatments.
转移性黑色素瘤对治疗有抗性，是皮肤癌中最具侵袭性的类型之一。microRNAs（miRNAs）最近被发现是对黑色素瘤具有治疗作用的新型分子。本研究专注于 miR-200a 在黑色素瘤进展中的作用和机制。
通过定量实时聚合酶链反应（qRT-PCR）检测 46 对黑色素瘤组织和癌旁标本中 miR-200a 的表达水平，并分析 miR-200a 水平与黑色素瘤患者预后临床特征的关系。通过 qRT-PCR 进一步验证黑色素瘤细胞中的 miR-200a 表达。此外，我们使用 TargetScan 鉴定了 miR-200a 的生物靶标。为了阐明 miR-200a 在黑色素瘤中抑制肿瘤的分子机制，我们进行了 Western blot 以确定 miR-200a 在 PI3K/Akt 通路和 EMT 中的功能。
qRT-PCR 分析表明黑色素瘤组织中 miR-200a 明显减少，与黑色素瘤患者不良预后和恶性临床病理特征相关。此外，功能分析表明 miR-200a 过表达显著抑制黑色素瘤细胞的增殖、侵袭和迁移能力。荧光素酶报告分析表明，高尔基膜蛋白 1（GOLM1）是黑色素瘤细胞中 miR-200a 的功能靶标。Western blot 分析表明，miR-200a 通过调节 PI3K/Akt 信号通路和上皮-间充质转化（EMT）抑制黑色素瘤的进展。还发现 miR-200a 上调显著抑制体内黑色素瘤肿瘤发生。所有这些数据表明，miR-200a 可作为黑色素瘤患者有前途的治疗靶点。
我们提供的证据表明，miR-200a 在黑色素瘤中下调，并通过抑制 GOLM1 表达和调节 PI3K/Akt 信号通路和 EMT 参与黑色素瘤的进展。miR-200a 水平降低与黑色素瘤患者预后不良相关。本研究的结果为理解黑色素瘤发病机制提供了新的见解，表明 miR-200a 可能作为黑色素瘤治疗的有前途的潜在治疗生物标志物。
