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长链非编码 RNA NEAT1 通过靶向 miR-152-3p/CDK6 轴促进黑色素瘤的进展:一项观察性研究。

Lnc NEAT1 facilitates the progression of melanoma by targeting the miR-152-3p/CDK6 axis: An observational study.

机构信息

Department of Medical Equipment, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Hunan, China.

Department of General Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Hunan, China.

出版信息

Medicine (Baltimore). 2024 Nov 1;103(44):e40379. doi: 10.1097/MD.0000000000040379.

Abstract

Long noncoding (Lnc) RNAs are novel regulators in melanoma. Lnc nuclear enriched autosomal transcript 1 (NEAT1) was reportedly upregulated in melanoma; however, the functional roles and mechanisms of Lnc NEAT1 need further investigation. Therefore, we used quantitative real-time PCR to determine the mRNA levels of Lnc NEAT1, miR-152-3p, and cyclin-dependent protein kinase 6 (CDK6). The protein level of CDK6 was determined by Western blot. Cell counting kit 8 and colony formation assays were used to assess cell proliferation. Cell migration was measured by wound healing and Transwell assays. Direct binding of the indicated molecules was verified by an RNA-binding protein immunoprecipitation assay and a dual luciferase reporter assay. The results revealed that Lnc NEAT1 and CDK6 were elevated, while miR-152-3p was downregulated in melanoma. Furthermore, Lnc NEAT1 was positively correlated with CDK6 expression and negatively correlated with miR-152-3p level. Furthermore, Lnc NEAT1 facilitated proliferation, migration, and invasion of melanoma cells. The underlying mechanism is that Lnc NEAT1 serves as a sponge for miR-152-3p to suppress the inhibitory effect of miR-152-3p on CDK6. Furthermore, the miR-152-3p/ CDK6 axis was implicated in the progression of melanoma accelerated by Lnc NEAT1. Taken together, Lnc NEAT1 may promote melanoma development by serving as an endogenous sponge of miR-152-3p, increasing CDK6 expression, and identifying a new target for the treatment of melanoma.

摘要

长链非编码 (Lnc) RNA 是黑色素瘤中的新型调节因子。据报道,核富集常染色体转录本 1 (NEAT1) 在黑色素瘤中上调;然而,Lnc NEAT1 的功能作用和机制仍需进一步研究。因此,我们使用定量实时 PCR 来确定 Lnc NEAT1、miR-152-3p 和细胞周期蛋白依赖性蛋白激酶 6 (CDK6) 的 mRNA 水平。CDK6 的蛋白水平通过 Western blot 确定。细胞计数试剂盒 8 和集落形成测定用于评估细胞增殖。通过划痕愈合和 Transwell 测定测量细胞迁移。通过 RNA 结合蛋白免疫沉淀测定和双荧光素酶报告基因测定验证了指示分子的直接结合。结果表明,Lnc NEAT1 和 CDK6 在黑色素瘤中升高,而 miR-152-3p 下调。此外,Lnc NEAT1 与 CDK6 表达呈正相关,与 miR-152-3p 水平呈负相关。此外,Lnc NEAT1 促进黑色素瘤细胞的增殖、迁移和侵袭。潜在机制是 Lnc NEAT1 作为 miR-152-3p 的海绵体,抑制 miR-152-3p 对 CDK6 的抑制作用。此外,Lnc NEAT1 加速的黑色素瘤进展涉及 miR-152-3p/CDK6 轴。总之,Lnc NEAT1 可能通过作为 miR-152-3p 的内源性海绵体,增加 CDK6 表达,为治疗黑色素瘤提供新的靶点,从而促进黑色素瘤的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d71f/11537649/7545ff81fa6b/medi-103-e40379-g001.jpg

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