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长链非编码RNA APTR扩增作为一种潜在的神经胶质瘤生物标志物，并通过miR-6734-5p/TCF7/LEF1轴促进神经胶质瘤进展。

LncRNA APTR amplification serves as a potential glioma biomarker and promotes glioma progression via miR-6734-5p/ TCF7/LEF1 axis.

作者信息

Chen Heng, Huang Mengzhen, Li Jiayi, Zhang Shanshan, Sun Cuiyun, Luo Wenjun, Yu Lin

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.

Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, Tianjin, 300070, China.

出版信息

Noncoding RNA Res. 2025 Feb 22;12:42-55. doi: 10.1016/j.ncrna.2025.02.007. eCollection 2025 Jun.

DOI:10.1016/j.ncrna.2025.02.007
PMID:40103614
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11914771/
Abstract

BACKGROUND: Alu-mediated p21 transcriptional regulator () overexpression is detected in different human cancers; however, few reports have investigated gene amplification conditions. Furthermore, whether amplification is related to glioma malignancy and the underlying mechanism remain unknown. METHODS: amplification and expression levels in 153 glioma samples were analyzed using qPCR. Correlations between APTR and patient prognosis were evaluated using Kaplan-Meier survival and COX regression analyses. Both and phenotypic assays were performed to confirm the carcinogenic effects of APTR in glioblastoma (GBM) cells. RNA-sequencing and RNA immunoprecipitation and luciferase reporter assays were performed to confirm APTR as a competing endogenous RNA (ceRNA) and to identify the downstream axis of APTR. RESULTS: Our results suggest that amplification and overexpression are novel independent diagnostic biomarkers for predicting poor prognosis in patients with gliomas. APTR knockdown significantly repressed the proliferation and invasion of GBM cells, both and . APTR was demonstrated to absorb miR-6734-5p and upregulate TCF7 and LEF1 expression. Taken together, these results suggest that APTR promotes the malignant phenotypes of GBM by inducing TCF7 and LEF1 expression. CONCLUSION: We identified APTR as a novel prognostic biomarker in patients with gliomas and confirmed that APTR is a ceRNA that promotes glioma progression via the APTR/miR-6734-5p/TCF7/LEF1 axis.

摘要

背景：在不同的人类癌症中检测到Alu介导的p21转录调节因子（）过表达；然而，很少有报告研究基因扩增情况。此外，扩增是否与胶质瘤恶性程度相关以及潜在机制仍不清楚。 方法：使用qPCR分析153例胶质瘤样本中的扩增和表达水平。采用Kaplan-Meier生存分析和COX回归分析评估APTR与患者预后的相关性。进行了APTR和TCF7/LEF1的表型分析，以证实APTR在胶质母细胞瘤（GBM）细胞中的致癌作用。进行RNA测序、RNA免疫沉淀和荧光素酶报告基因检测，以证实APTR作为竞争性内源性RNA（ceRNA）并确定APTR的下游轴。 结果：我们的结果表明，扩增和过表达是预测胶质瘤患者预后不良的新型独立诊断生物标志物。APTR敲低显著抑制了GBM细胞的增殖和侵袭，包括APTR和TCF7/LEF1。证明APTR吸收miR-6734-5p并上调TCF7和LEF1的表达。综上所述，这些结果表明APTR通过诱导TCF7和LEF1的表达促进GBM的恶性表型。 结论：我们确定APTR是胶质瘤患者的一种新型预后生物标志物，并证实APTR是一种ceRNA，它通过APTR/miR-6734-5p/TCF7/LEF1轴促进胶质瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/b75d8b769a59/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/cc5f06dcb181/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/8767601361de/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/fe34c283cd8f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/5acdb4b663fc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/ea09c9e8e297/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/7dfd09d492ab/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/febc3dda144b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/49279da7847f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/a6886a90a2b8/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/0186f47790ce/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/9698c7ce4e5e/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/f44e4b658bf1/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/b75d8b769a59/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/cc5f06dcb181/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/8767601361de/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/fe34c283cd8f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/5acdb4b663fc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/ea09c9e8e297/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/7dfd09d492ab/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/febc3dda144b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/49279da7847f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/a6886a90a2b8/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/0186f47790ce/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/9698c7ce4e5e/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/f44e4b658bf1/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758c/11914771/b75d8b769a59/mmcfigs5.jpg

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本文引用的文献

[1]
Expression and Significance of the Long Non-Coding RNA APTR in the Occurrence and Development of Lung Adenocarcinoma.

J Environ Pathol Toxicol Oncol. 2025

[2]
TC2N Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Targeting the Wnt/β-Catenin Signaling Pathway.

Lab Invest. 2023-12

[3]
National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Lancet Reg Health West Pac. 2023-2-21

[4]
N6-Methyladenosine-Mediated Up-Regulation of FZD10 Regulates Liver Cancer Stem Cells' Properties and Lenvatinib Resistance Through WNT/β-Catenin and Hippo Signaling Pathways.

Gastroenterology. 2023-5

[5]
Low expression of lncRNA APTR promotes gastric cancer progression.

Transl Oncol. 2022-11

[6]
PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK.

Int J Biol Sci. 2022

[7]
Moving pan-cancer studies from basic research toward the clinic.

Nat Cancer. 2021-9

[8]
Nitazoxanide and Cancer Drug Resistance: Targeting Wnt/β-catenin Signaling Pathway.

Arch Med Res. 2022-4

[9]
LncRNA APTR Promotes Uterine Leiomyoma Cell Proliferation by Targeting ERα to Activate the Wnt/β-Catenin Pathway.

Front Oncol. 2021-3-10

[10]
Targeting the Wnt/β-catenin signaling pathway in cancer.

J Hematol Oncol. 2020-12-4

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