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长链非编码 RNA 467 通过 microRNA-128-3p/血管内皮生长因子 C 轴促进结直肠癌的肿瘤进展和血管生成。

Long intergenic non-protein-coding RNA 467 promotes tumor progression and angiogenesis via the microRNA-128-3p/vascular endothelial growth factor C axis in colorectal cancer.

机构信息

Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Bioengineered. 2022 May;13(5):12392-12408. doi: 10.1080/21655979.2022.2074666.

DOI:10.1080/21655979.2022.2074666
PMID:35587748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9275949/
Abstract

Long non-coding RNAs (lncRNAs) are important regulators and biomarkers of tumorigenesis and tumor metastasis. Long intergenic non-protein-coding RNA 467 (LINC00467) is associated with various cancers. However, the role and mechanism of LINC00467 in colorectal cancer (CRC) promotion are poorly understood. This study aimed to present new details of LINC00467 in the progression of CRC. Reverse transcription-polymerase chain reaction demonstrated that the expression level of LINC00467 in CRC tissues and cell lines was significantly upregulated, which was closely related to the clinical features of CRC. Cell and animal studies showed that the downregulation of LINC00467 expression in CRC cells significantly inhibited cell proliferation, metastasis, and angiogenesis. Moreover, the overexpression of LINC00467 accelerated CRC promotion. Bioinformatics analysis and luciferase reporter assay confirmed that LINC00467 binds to miR-128-3p. Rescue experiments manifested that decreased miR-128-3p level reversed CRC cell inhibition by silencing LINC00467. Furthermore, vascular endothelial growth factor C (VEGFC) was identified as a target of miR-128-3p that could reverse the inhibition of cell growth that is mediated by miR-128-3p. Altogether, our results showed that LINC00467 contributes to CRC progression and angiogenesis via the miR-128-3p/VEGFC axis. Our findings expand the understanding of the mechanisms underlying CRC and suggest potential targets for clinical strategies against CRC.

摘要

长非编码 RNA(lncRNA)是肿瘤发生和转移的重要调节因子和生物标志物。长基因间非蛋白编码 RNA 467(LINC00467)与多种癌症有关。然而,LINC00467 在结直肠癌(CRC)促进中的作用和机制尚不清楚。本研究旨在阐述 LINC00467 在 CRC 进展中的新细节。逆转录-聚合酶链反应显示,LINC00467 在 CRC 组织和细胞系中的表达水平显著上调,与 CRC 的临床特征密切相关。细胞和动物研究表明,CRC 细胞中 LINC00467 表达的下调显著抑制细胞增殖、转移和血管生成。此外,LINC00467 的过表达加速了 CRC 的促进。生物信息学分析和荧光素酶报告基因检测证实 LINC00467 与 miR-128-3p 结合。挽救实验表明,降低 miR-128-3p 水平可逆转沉默 LINC00467 对 CRC 细胞的抑制作用。此外,血管内皮生长因子 C(VEGFC)被鉴定为 miR-128-3p 的靶基因,可逆转 miR-128-3p 介导的细胞生长抑制作用。总之,我们的研究结果表明,LINC00467 通过 miR-128-3p/VEGFC 轴促进 CRC 的进展和血管生成。我们的研究结果扩展了对 CRC 发生机制的理解,并为针对 CRC 的临床策略提供了潜在的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/993b3b059986/KBIE_A_2074666_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/432cbf0ba8e1/KBIE_A_2074666_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/afb3eb3141ed/KBIE_A_2074666_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/e902d23f628b/KBIE_A_2074666_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/bbd106ba657e/KBIE_A_2074666_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/032edd3eae18/KBIE_A_2074666_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/751dbf551096/KBIE_A_2074666_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/1d39fc92e276/KBIE_A_2074666_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/5ec0f98fd526/KBIE_A_2074666_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/993b3b059986/KBIE_A_2074666_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/432cbf0ba8e1/KBIE_A_2074666_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/afb3eb3141ed/KBIE_A_2074666_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/e902d23f628b/KBIE_A_2074666_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/bbd106ba657e/KBIE_A_2074666_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/032edd3eae18/KBIE_A_2074666_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/751dbf551096/KBIE_A_2074666_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/1d39fc92e276/KBIE_A_2074666_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/5ec0f98fd526/KBIE_A_2074666_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e04/9275949/993b3b059986/KBIE_A_2074666_F0008_OC.jpg

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