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LncRNA MIR155HG 在黑色素瘤细胞中受 SP1 上调并驱动黑色素瘤进展,调节 miR-485-3p/PSIP1 轴。

The LncRNA MIR155HG is Upregulated by SP1 in Melanoma Cells and Drives Melanoma Progression Modulating the MiR-485-3p/PSIP1 Axis.

机构信息

Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.

出版信息

Anticancer Agents Med Chem. 2022;22(1):152-159. doi: 10.2174/1871520621666210322092906.

Abstract

BACKGROUND

MIR155HG is a long non-coding RNA (lncRNA) that has been shown to be dysregulated in a range of tumor types, but the functions of this lncRNA in melanoma remain to be explored.

OBJECTIVES

We explored the functions of lncRNA MIR155HG in melanoma progression.

METHODS

The expression of miR155HG was analyzed in clinical melanoma. Bioinformatics analysis was performed to assess the potential tumor-related functions of miR155HG. The interaction of miR155HG and SP1 and the inhibition of PSIP1 by miR-485-3p were analyzed by ChIP, luciferase reporter experiments, and the biological effects in melanoma were explored by colony formation assays, EdU cell proliferation assays, Transwell analysis, and intracranial melanoma mouse model.

RESULTS

Herein, we found that MIR155HG was markedly upregulated in melanoma cell lines and tissues. We further determined that the SP1 transcription factor was responsible for driving MIR155HG upregulation in melanoma. Elevated MIR155HG levels were linked to decreased overall survival (OS) in melanoma patients, and we further determined that MIR155HG expression was an independent predictor of melanoma patient prognosis. When MIR155HG was knocked down in melanoma cells, this impaired their proliferative, migratory, and invasive activity. By using predictive bioinformatics analyses, we identified miR-485-3p as a microRNA (miRNA) capable of binding to both MIR155HG and the 3' UTR of PSIP1.

CONCLUSION

Together, these results suggest that MIR155HG is capable of promoting melanoma cell proliferation via the miR-485-3p/PSIP1 axis. These novel findings provide new insights into the development of melanoma, potentially highlighting future avenues for therapeutic intervention.

摘要

背景

MIR155HG 是一种长链非编码 RNA(lncRNA),已在多种肿瘤类型中显示出失调,但该 lncRNA 在黑色素瘤中的功能仍有待探索。

目的

我们探讨了 lncRNA MIR155HG 在黑色素瘤进展中的作用。

方法

分析临床黑色素瘤中 miR155HG 的表达。通过生物信息学分析评估 miR155HG 的潜在肿瘤相关功能。通过 ChIP、荧光素酶报告实验分析 miR155HG 与 SP1 的相互作用以及 PSIP1 被 miR-485-3p 抑制的情况,并通过集落形成实验、EdU 细胞增殖实验、Transwell 分析和颅内黑色素瘤小鼠模型探讨其在黑色素瘤中的生物学效应。

结果

本研究发现 MIR155HG 在黑色素瘤细胞系和组织中明显上调。进一步确定 SP1 转录因子负责驱动黑色素瘤中 MIR155HG 的上调。升高的 MIR155HG 水平与黑色素瘤患者总生存期(OS)降低相关,我们进一步确定 MIR155HG 表达是黑色素瘤患者预后的独立预测因子。当黑色素瘤细胞中的 MIR155HG 被敲低时,其增殖、迁移和侵袭活性受损。通过使用预测性生物信息学分析,我们确定 miR-485-3p 是一种能够与 MIR155HG 和 PSIP1 的 3'UTR 结合的 microRNA(miRNA)。

结论

综上所述,这些结果表明 MIR155HG 能够通过 miR-485-3p/PSIP1 轴促进黑色素瘤细胞增殖。这些新发现为黑色素瘤的发展提供了新的见解,可能为治疗干预提供新的途径。

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