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CASC21,一种 FOXP1 诱导的长非编码 RNA,通过调节 CDK6 促进结直肠癌的生长。

CASC21, a FOXP1 induced long non-coding RNA, promotes colorectal cancer growth by regulating CDK6.

机构信息

Oncology, Nanjing Hospital of Chinese Medicine, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu, China.

Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu, China.

出版信息

Aging (Albany NY). 2020 Jun 25;12(12):12086-12106. doi: 10.18632/aging.103376.

DOI:10.18632/aging.103376
PMID:32584787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7343488/
Abstract

Emerging studies indicate that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we reported lncRNA CASC21, which is induced by FOXP1, functions as an oncogene in CRC. We systematically elucidated its clinical significance and possible molecular mechanism in CRC. LncRNA expression in CRC was analyzed by RNA-sequencing data in TCGA. The expression level of CASC21 in tissues was determined by qRT-PCR. The functions of CASC21 was investigated by and assays (CCK8 assay, colony formation assay, EdU assay, xenograft model, flow cytometry assay, immunohistochemistry (IHC) and Western blot). Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP) and luciferase reporter assays were utilized to demonstrate the potential mechanisms of CASC21. CASC21 is overexpressed in CRC and high CASC21 expression is associated with poor survival. Functional experiments revealed that CASC21 promotes CRC cell growth. Mechanistically, we found that CASC21 expressed predominantly in the cytoplasm. CASC21 could interact with miR-539-5p and regulate its target CDK6. Together, our study elucidated that CASC21 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.

摘要

新兴研究表明,长非编码 RNA(lncRNA)在结直肠癌(CRC)中发挥着关键作用。在这里,我们报道了受 FOXP1 诱导的 lncRNA CASC21,它在 CRC 中作为癌基因发挥作用。我们系统地阐明了其在 CRC 中的临床意义和可能的分子机制。通过 TCGA 的 RNA-seq 数据分析 CRC 中的 lncRNA 表达。通过 qRT-PCR 测定组织中 CASC21 的表达水平。通过 CCK8 测定、集落形成测定、EdU 测定、异种移植模型、流式细胞术测定、免疫组织化学(IHC)和 Western blot 研究 CASC21 的功能。染色质免疫沉淀(ChIP)、RNA 免疫沉淀(RIP)和荧光素酶报告基因测定用于证明 CASC21 的潜在机制。CASC21 在 CRC 中过表达,高 CASC21 表达与不良生存相关。功能实验表明 CASC21 促进 CRC 细胞生长。机制上,我们发现 CASC21 主要在细胞质中表达。CASC21 可以与 miR-539-5p 相互作用并调节其靶标 CDK6。总之,我们的研究阐明了 CASC21 在 CRC 中作为癌基因的作用,它可能成为 CRC 诊断和治疗的新靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de9/7343488/fbad8a1b5bae/aging-12-103376-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de9/7343488/a9db2eef5af1/aging-12-103376-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de9/7343488/f59bdd0f8c0a/aging-12-103376-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de9/7343488/fbad8a1b5bae/aging-12-103376-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de9/7343488/f2924f182b82/aging-12-103376-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de9/7343488/fbad8a1b5bae/aging-12-103376-g007.jpg

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