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原发性皮肤恶性黑素瘤、皮肤恶性黑素瘤转移灶和良性黑素细胞痣中的 miRNA 机制。

The miRNA machinery in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases and benign melanocytic nevi.

机构信息

Department of Dermatology, Venereology and Allergology, Ruhr-University Bochum, St. Josef Hospital, Gudrunstr. 56, 44791 Bochum, Germany.

出版信息

Cell Tissue Res. 2012 Oct;350(1):119-26. doi: 10.1007/s00441-012-1446-0. Epub 2012 Jun 17.

Abstract

Although several studies have shown a dysregulation of microRNA (miRNA) expression profiles in cutaneous melanoma, there has been little research on the miRNA machinery itself. In this study, we investigated the mRNA expression profiles of different miRNA machinery components in primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic nevi (BMN). Patients with PCMM (n = 7), CMMM (n = 6) and BMN (n = 7) were included in the study. Punch biopsies were harvested from the centers of tumors (lesional) and from BMN (control). In contrast to previous reports exploring specific clusters of miRNAs in PCMM, the present study investigates mRNA expression levels of Dicer, Drosha, Exp5, DGCR8 and the RISC components PACT, argonaute-1, argonaute-2, TARBP1, TARBP2, MTDH and SND1, which were detected by TaqMan real-time reverse transcription polymerase chain reaction (RT-PCR). Argonaute-1, TARBP2 and SND1 expression levels were significantly higher in BMN compared to PCMM (p < 0.05). TARBP2 expression levels were significantly higher in CMMM compared to PCMM (p < 0.05). SND1 expression levels were significantly higher in CMMM compared to PCMM and BMN (p < 0.05). Dicer, Drosha, DGCR8, Exp5, argonaute-2, PACT, TARBP1 and MTDH expression levels showed no significant differences within groups (p > 0.05). The results of this study show that the miRNA machinery components argonaute-1, TARBP2 and SND1 are dysregulated in PCMM and CMMM compared to BMN and may play a role in the process of malignant transformation.

摘要

尽管已有几项研究表明,皮肤黑色素瘤中存在 microRNA(miRNA)表达谱的失调,但对 miRNA 机制本身的研究却很少。在这项研究中,我们研究了原发性皮肤恶性黑色素瘤(PCMM)、皮肤恶性黑色素瘤转移(CMMM)和良性黑色素细胞痣(BMN)中不同 miRNA 机制成分的 mRNA 表达谱。纳入了 7 例 PCMM 患者、6 例 CMMM 患者和 7 例 BMN 患者。从肿瘤中心(病变)和 BMN(对照)采集了皮肤活检标本。与以前探索 PCMM 中特定 miRNA 簇的报告不同,本研究通过 TaqMan 实时逆转录聚合酶链反应(RT-PCR)检测了 Dicer、Drosha、Exp5、DGCR8 以及 RISC 成分 PACT、argonaute-1、argonaute-2、TARBP1、TARBP2、MTDH 和 SND1 的 mRNA 表达水平。与 PCMM 相比,BMN 中 argonaute-1、TARBP2 和 SND1 的表达水平显著更高(p<0.05)。与 PCMM 相比,CMMM 中 TARBP2 的表达水平显著更高(p<0.05)。与 PCMM 和 BMN 相比,CMMM 中 SND1 的表达水平显著更高(p<0.05)。Dicer、Drosha、DGCR8、Exp5、argonaute-2、PACT、TARBP1 和 MTDH 的表达水平在各组之间无显著差异(p>0.05)。本研究结果表明,与 BMN 相比,miRNA 机制成分 argonaute-1、TARBP2 和 SND1 在 PCMM 和 CMMM 中失调,可能在恶性转化过程中发挥作用。

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