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黑素细胞和黑色素瘤细胞中差异表达的 circRNAs 及其对细胞增殖和侵袭的影响。

Differentially expressed circRNAs in melanocytes and melanoma cells and their effect on cell proliferation and invasion.

机构信息

Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Department of Plastic and Reconstructive Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Oncol Rep. 2018 Apr;39(4):1813-1824. doi: 10.3892/or.2018.6263. Epub 2018 Feb 13.

Abstract

Circular RNAs (circRNAs) play critical roles in the occurrence of human diseases, including cancer. However, the detailed functions of circRNAs in melanoma have not been fully elucidated. In the present study, a circRNA microarray was performed to analyze the variability of circRNAs in the low-metastatic melanoma WM35 cell line and in the high-metastatic melanoma WM451 cell line in comparison to control human melanocytes. The results revealed that five circRNAs were upregulated and four circRNAs were downregulated in both the WM35 and WM451 cells. qRT-PCR revealed an upregulated expression of circ0000082 and circ0016418 and a downregulation of circ0023988, circ0008157 and circ0030388 in the cells which was consistent with the results of the microarray assay. Functional tests revealed that knockdown of circ0023988, circ0008157 or circ0030388 significantly promoted the proliferation and invasion of the WM35 cells. Following the silencing of circ0000082 or circ0016418 in WM451 cells, the proliferation and invasion of the WM451 cells were inhibited. Bioinformatic analysis predicted that the circ0000082-, circ0023988- and circ0008157-circRNA-miRNA-mRNA network may participate in the occurrence, development, invasion and metastasis of malignant tumors. The present study revealed several differentially expressed circRNAs, indicating that the newly identified circRNAs may provide new therapeutic targets for melanoma.

摘要

环状 RNA(circRNAs)在人类疾病的发生中发挥着关键作用,包括癌症。然而,circRNAs 在黑色素瘤中的详细功能尚未完全阐明。在本研究中,通过circRNA 微阵列分析比较低转移性黑色素瘤 WM35 细胞系和高转移性黑色素瘤 WM451 细胞系与对照人黑素细胞中 circRNAs 的变异性。结果显示,在 WM35 和 WM451 细胞中,有 5 个 circRNAs 上调,4 个 circRNAs 下调。qRT-PCR 显示 circ0000082 和 circ0016418 的表达上调,circ0023988、circ0008157 和 circ0030388 的表达下调,与微阵列检测结果一致。功能试验显示,circ0023988、circ0008157 或 circ0030388 的敲低显著促进了 WM35 细胞的增殖和侵袭。在 WM451 细胞中沉默 circ0000082 或 circ0016418 后,WM451 细胞的增殖和侵袭受到抑制。生物信息学分析预测,circ0000082-、circ0023988-和 circ0008157-circRNA-miRNA-mRNA 网络可能参与恶性肿瘤的发生、发展、侵袭和转移。本研究发现了几个差异表达的 circRNAs,表明新鉴定的 circRNAs 可能为黑色素瘤提供新的治疗靶点。

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