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沉默长链非编码 RNA LINC01133 通过调控 microRNA-1299 依赖的 IGF2BP3 抑制胰腺癌。

Silencing long noncoding RNA LINC01133 suppresses pancreatic cancer through regulation of microRNA-1299-dependent IGF2BP3.

机构信息

Clinical Laboratory, Huadu District People's Hospital of Guangzhou, Guangzhou, People's Republic of China.

Clinical Laboratory, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.

出版信息

J Biochem Mol Toxicol. 2024 Jan;38(1):e23534. doi: 10.1002/jbt.23534. Epub 2023 Sep 17.

Abstract

The deregulation of long noncoding RNAs (lncRNAs) holds great potential in the treatment of multiple cancers, including pancreatic cancer (PC). However, the specific molecular mechanisms by which LINC01133 contributes to pancreatic cancer remain unknown. Subsequent to bioinformatics analysis, we predicted and analyzed differentially expressed lncRNAs, microRNAs, and genes in pancreatic cancer. We determined the expression patterns of LINC01133, miR-1299, and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in pancreatic cancer cells, and validated their interactions through luciferase reporter and RNA immunoprecipitation assays. We implemented loss-of-function and gain-of-function experiments for LINC01133, miR-1299, and IGF2BP3 to assay their potential effects on pancreatic cancer cell functions. We observed high expression of LINC01133 and IGF2BP3, but low expression of miR-1299, in pancreatic cancer cells. Furthermore, we found that LINC01133 enhances IGF2BP3 through binding with miR-1299. Silencing LINC01133 or IGF2BP3 and/or overexpressing miR-1299 limited pancreatic cancer cell proliferation, invasion, epithelial-mesenchymal transition, and suppressed tumorigenic abilities in mice lacking T cells (nude mice). Overall, our findings identified that silencing LINC01133 downregulates IGF2BP3 by upregulating miR-1299 expression, ultimately leading to the prevention of pancreatic cancer.

摘要

长链非编码 RNA(lncRNA)的失调在多种癌症的治疗中具有巨大的潜力,包括胰腺癌(PC)。然而,LINC01133 促进胰腺癌的具体分子机制尚不清楚。在生物信息学分析之后,我们预测和分析了胰腺癌中差异表达的 lncRNA、microRNA 和基因。我们确定了 LINC01133、miR-1299 和胰岛素样生长因子 2 mRNA 结合蛋白 3(IGF2BP3)在胰腺癌细胞中的表达模式,并通过荧光素酶报告和 RNA 免疫沉淀测定验证了它们的相互作用。我们对 LINC01133、miR-1299 和 IGF2BP3 进行了功能丧失和获得功能实验,以检测它们对胰腺癌细胞功能的潜在影响。我们观察到胰腺癌细胞中 LINC01133 和 IGF2BP3 表达升高,而 miR-1299 表达降低。此外,我们发现 LINC01133 通过与 miR-1299 结合来增强 IGF2BP3。沉默 LINC01133 或 IGF2BP3 和/或过表达 miR-1299 可限制缺乏 T 细胞(裸鼠)的胰腺癌细胞增殖、侵袭、上皮-间充质转化,并抑制肿瘤发生能力。总的来说,我们的研究结果表明,沉默 LINC01133 通过上调 miR-1299 表达下调 IGF2BP3,最终预防胰腺癌的发生。

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