通过靶向 PTEN 通路调控结直肠癌的转移和生长:LncRNA MLLT4-AS1 的最新进展。

Ruipeng Liang, Zhili Liu, Bo Li, Debing Xiang, Chunrong Wu
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引用次数: 0

摘要

背景:在全球范围内,结直肠癌(CRC)是导致死亡的主要原因。最近的研究表明,长非编码 RNA(lncRNA)对评估 CRC 患者的生存率至关重要。然而,新型 lncRNA MLLT4-AS1 在 CRC 中的功能尚不清楚:本研究旨在确定 lncRNA MLLT4-AS1 在 CRC 中的表达及其临床意义:方法:通过TCGA数据库评估MLLT4-AS1在CRC中的表达水平。通过 RT qPCR 分析评估了 MLLT4-AS1 在 CRC 细胞系中的相对水平。在细胞培养中,用 MLLT4-AS1 siRNA、阴性对照、过表达 MLLT4-AS1 或 PTEN 质粒转染 HT29 细胞。流式细胞术、CCK 8 检测法、伤口愈合分析法和透孔试验分别用于量化细胞凋亡、细胞繁殖、迁移和侵袭。为了评估 MLLT4-AS1 质粒在体内对肿瘤生长的影响,我们建立了裸鼠异种移植模型。利用 RNA pull-down 分析寻找 MLLT4-AS1 的可能靶点:结果:MLLT4-AS1 在 CRC 细胞系和患者体内显著增加。结果:MLLT4-AS1 在 CRC 细胞系和患者中大量增加,它抑制了 CRC 细胞的凋亡,并加速了它们的增殖、迁移和侵袭特性。在体内分析中,MLLT4-AS1 还增强了 CRC 细胞的转移和增殖。通过 RNA pull -- down 分析发现,生物素标记的 PTEN 被大量富集。MLLT4-AS1通过泛素化蛋白酶体依赖性RNA降解抑制了磷酸酶和PTEN的表达。因此,PTEN被认为是MLLT4-AS1的一个潜在靶点。通过靶向 PTEN,MLLT4-AS1 强化了恶性 CRC 的生物学行为:结论:研究认为,MLLT4-AS1/PTEN 轴可能是针对 CRC 患者的一种创新性治疗干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Regulation of Metastasis and Growth of Colorectal Cancer via Targeting the PTEN Pathway: An Update on the Progress of LncRNA MLLT4-AS1.

Background: Globally, colorectal cancer (CRC) is known as the primary cause of mortality. Recent studies have reported that long non-coding RNAs (lncRNAs) are essential in assessing the survival of CRC patients. However, the function of the novel lncRNA MLLT4-AS1 in CRC is still unknown.

Objective: This study aimed to identify the expression and the clinical significance of lncRNA MLLT4-AS1 in CRC.

Methods: The level of MLLT4-AS1 in CRC was evaluated via the TCGA database. The relative level of MLLT4-AS1 in CRC cell lines was assessed by RT qPCR analysis. In cell culture, HT29 cells were transfected with MLLT4-AS1 siRNA, negative control, overexpressed MLLT4-AS1, or PTEN plasmids. Flow cytometry, CCK 8 assay, wound healing analysis, and transwell assay were used to quantify apoptosis, cell propagation, migration, and invasion, respectively. A nude mouse xenograft model was developed to evaluate the in vivo impact of MLLT4-AS1 plasmids on tumor growth. RNA pull-down analysis was used to search for possible targets of MLLT4-AS1.

Results: MLLT4-AS1 was substantially increased in CRC cell lines and patients. It inhibited CRC cell apoptosis and accelerated their proliferative, migration, and invasive properties. In in vivo analysis, MLLT4-AS1 also enhanced the metastasis and proliferation of CRC cells. It was found that PTEN was substantially enriched by biotin-labeled PTEN, as identified via an RNA pull-- down analysis. The expression of phosphatase and PTEN was suppressed by MLLT4-AS1 by ubiquitination proteasome-dependent RNA degradation. Thus, PTEN is considered a potential target of MLLT4-AS1. By targeting PTEN, MLLT4-AS1 intensified the biological behavior of malignant CRC.

Conclusion: The study concluded that the MLLT4-AS1/PTEN axis may represent an innovative therapeutic intervention for CRC patients.

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