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结直肠癌中特定上调的长非编码 RNA 促进癌症进展。

A specific upregulated long noncoding RNA in colorectal cancer promotes cancer progression.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China.

School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan, China.

出版信息

JCI Insight. 2022 Aug 8;7(15):e158855. doi: 10.1172/jci.insight.158855.

Abstract

Long noncoding RNA (lncRNA) plays a crucial role in the pathogenesis of various diseases, including colorectal cancer (CRC). The gene mutations of adenomatous polyposis coli (APC) were found in most patients with CRC. They function as important inducers of tumorigenesis. Based on our microarray results, we identified a specific upregulated lncRNA in CRC (SURC). Further analysis showed that high SURC expression correlated with poorer disease-free survival and overall survival in patients with CRC. Furthermore, we found that mutated APC genes can promote the transcription of SURC by reducing the degradation of β-catenin protein in CRC. Functional assays revealed that knockdown of SURC impaired CRC cell proliferation, colony formation, cell cycle, and tumor growth. Additionally, SURC promotes CCND2 expression by inhibiting the expression of miR-185-5p in CRC cells. In conclusion, we demonstrate that SURC is a specific upregulated lncRNA in CRC and the SURC/miR-185-5p/CCND2 axis may be targetable for CRC diagnosis and therapy.

摘要

长链非编码 RNA(lncRNA)在多种疾病的发病机制中发挥着关键作用,包括结直肠癌(CRC)。大多数 CRC 患者中发现了腺瘤性结肠息肉病(APC)的基因突变。它们作为肿瘤发生的重要诱导物发挥作用。基于我们的微阵列结果,我们在 CRC 中鉴定出一种特定的上调 lncRNA(SURC)。进一步分析表明,CRC 中高 SURC 表达与患者无病生存期和总生存期较差相关。此外,我们发现突变型 APC 基因可以通过减少 CRC 中 β-连环蛋白蛋白的降解来促进 SURC 的转录。功能测定显示,SURC 的敲低会损害 CRC 细胞的增殖、集落形成、细胞周期和肿瘤生长。此外,SURC 通过抑制 CRC 细胞中 miR-185-5p 的表达来促进 CCND2 的表达。总之,我们证明 SURC 是 CRC 中一种特异性上调的 lncRNA,并且 SURC/miR-185-5p/CCND2 轴可能是 CRC 诊断和治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016a/9462503/949f45ef0c96/jciinsight-7-158855-g001.jpg

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