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长非编码 RNA TGLC15 通过稳定 Sox4 促进肝细胞癌。

Long non-coding RNA TGLC15 advances hepatocellular carcinoma by stabilizing Sox4.

机构信息

Department of General Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

出版信息

J Clin Lab Anal. 2020 Jan;34(1):e23009. doi: 10.1002/jcla.23009. Epub 2019 Sep 8.

DOI:10.1002/jcla.23009
PMID:31495979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6977111/
Abstract

BACKGROUND

The hepatocellular carcinoma (HCC) belongs to a common malignancy especially in China. Recent data have clarified important roles of long non-coding RNAs (lncRNAs) in HCC. However, the role of a novel intergenic lncRNA termed TGLC15 is still elusive.

METHODS

We screened for novel lncRNAs using lncRNA profiling. TGLC15 expression was quantified by qRT-PCR. In vitro experiments such as migration and viability assays were performed. In vivo implantation experiments were conducted to investigate tumorigenic functions of TGLC15. Combined RNA immunoprecipitation (RIP) and mass spectrometry (MS) were utilized to uncover Sox4 as TGLC15 binding protein.

RESULTS

TGLC15 is significantly overexpressed in tumor tissues and HCC cell lines. Higher TGLC15 levels correlated with advanced malignant characteristics such as TNM stages, tumor size, and metastasis. TGLC15 advanced HCC migration and viability. The in vivo experiments supported that xenograft tumor growth and proliferation were facilitated by TGLC15 overexpression. Mechanistic studies showed that TGLC15 interacted with Sox4 and interaction between TGLC15 and Sox4 could stabilize Sox4 via reduction in proteasome-mediated degradation.

CONCLUSIONS

Collectively, our data have identified a novel lncRNA TGLC15 during HCC development. The TGLC15-Sox4 signaling might be a potential target for pharmaceutical intervention.

摘要

背景

肝细胞癌(HCC)属于一种常见的恶性肿瘤,尤其在中国。最近的数据阐明了长非编码 RNA(lncRNA)在 HCC 中的重要作用。然而,一种新型的基因间 lncRNA,称为 TGLC15,其作用仍不清楚。

方法

我们使用 lncRNA 谱筛选新的 lncRNA。通过 qRT-PCR 定量检测 TGLC15 的表达。进行体外实验,如迁移和活力测定。进行体内植入实验以研究 TGLC15 的致瘤功能。联合 RNA 免疫沉淀(RIP)和质谱(MS)用于揭示 Sox4 是 TGLC15 的结合蛋白。

结果

TGLC15 在肿瘤组织和 HCC 细胞系中显著过表达。较高的 TGLC15 水平与晚期恶性特征相关,如 TNM 分期、肿瘤大小和转移。TGLC15 促进 HCC 的迁移和活力。体内实验支持 TGLC15 过表达促进异种移植肿瘤的生长和增殖。机制研究表明,TGLC15 与 Sox4 相互作用,通过减少蛋白酶体介导的降解来稳定 Sox4。

结论

总的来说,我们的数据在 HCC 发展过程中鉴定了一种新型 lncRNA TGLC15。TGLC15-Sox4 信号可能是药物干预的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/355ab7ee8828/JCLA-34-e23009-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/174551eb30a4/JCLA-34-e23009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/fec81d9b1210/JCLA-34-e23009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/caa63788f439/JCLA-34-e23009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/dcbcc947ae2b/JCLA-34-e23009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/355ab7ee8828/JCLA-34-e23009-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/174551eb30a4/JCLA-34-e23009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/fec81d9b1210/JCLA-34-e23009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/caa63788f439/JCLA-34-e23009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/dcbcc947ae2b/JCLA-34-e23009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1457/6977111/355ab7ee8828/JCLA-34-e23009-g005.jpg

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