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MYC 激活的长链非编码 RNA HNF1A-AS1 通过与 miR-32-5p/SOX4 轴合作促进胶质瘤进展。

MYC-activated lncRNA HNF1A-AS1 overexpression facilitates glioma progression via cooperating with miR-32-5p/SOX4 axis.

机构信息

Department of Neurosurgery, Gaozhou People's Hospital, Gaozhou, Guangdong, China.

Department of Radiation Oncology, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

出版信息

Cancer Med. 2020 Sep;9(17):6387-6398. doi: 10.1002/cam4.3186. Epub 2020 Jul 20.

DOI:10.1002/cam4.3186
PMID:33448691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7476832/
Abstract

Mounting literatures have revealed the crucial effects of long noncoding RNA (lncRNA) in various cancers, including glioma. HNF1A-AS1, a novel lncRNA, is reported to modulate tumorigenesis and development of multiple cancers. However, the tumorigenic function of lncRNA HNF1A-AS1 in glioma remains largely unknown. quantitative reverse transcription and polymerase chain reaction and western blot assays were applied to evaluate the expression of relevant mRNAs and proteins. 5-Ethynyl-2'- deoxyuridine, terminal deoxynucleotidyl transferase dUTP nick-end labeling, flow cytometry, and transwell assays were conducted for examining the influence of HNF1A-AS1 on glioma cell functions. The relationship among RNAs was investigated by mechanical experiments. The results demonstrated that HNF1A-AS1 was predominantly highly expressed in glioma cell lines compared with nontumor glial epithelial cell, which was associated with the stimulation of transcription factor myelocytomatosis oncogene. Knockdown of HNF1A-AS1 remarkably inhibited glioma cells proliferation, migration, and invasion, while accelerating cell apoptosis in vitro. Mechanically, HNF1A-AS1 served as a miR-32-5p sponge. Moreover, SOX4 was discovered as a target of miR-32-5p. Inhibited miR-32-5p or upregulated SOX4 could markedly counteract the inhibitory effects of silencing HNF1A-AS1 on glioma malignant biological behaviors. HNF1A-AS1 exerted oncogenic property in glioma progression via upregulating miR-32-5p-mediated SOX4 expression, suggesting potential novel therapeutic target for future glioma treatment.

摘要

越来越多的文献表明长链非编码 RNA（lncRNA）在包括神经胶质瘤在内的各种癌症中具有重要作用。HNF1A-AS1 是一种新型 lncRNA，据报道可调节多种癌症的肿瘤发生和发展。然而，lncRNA HNF1A-AS1 在神经胶质瘤中的致瘤功能仍知之甚少。应用定量逆转录聚合酶链反应和 Western blot 检测相关 mRNA 和蛋白的表达。5-乙炔基-2'-脱氧尿苷、末端脱氧核苷酸转移酶 dUTP 缺口末端标记、流式细胞术和 Transwell 检测用于研究 HNF1A-AS1 对神经胶质瘤细胞功能的影响。通过力学实验研究 RNA 之间的关系。结果表明，与非肿瘤神经胶质上皮细胞相比，HNF1A-AS1 在神经胶质瘤细胞系中表达明显升高，这与转录因子髓细胞瘤癌基因的刺激有关。HNF1A-AS1 敲低显著抑制神经胶质瘤细胞的增殖、迁移和侵袭，同时促进体外细胞凋亡。在机制上，HNF1A-AS1 作为 miR-32-5p 的海绵。此外，发现 SOX4 是 miR-32-5p 的靶标。抑制 miR-32-5p 或上调 SOX4 可以显著抵消沉默 HNF1A-AS1 对神经胶质瘤恶性生物学行为的抑制作用。HNF1A-AS1 通过上调 miR-32-5p 介导的 SOX4 表达发挥致癌作用，提示未来神经胶质瘤治疗的潜在新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/e91619bf4cfa/CAM4-9-6387-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/80510050838e/CAM4-9-6387-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/fdb18a0cd646/CAM4-9-6387-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/963e0db8e3c3/CAM4-9-6387-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/681c2bfbe602/CAM4-9-6387-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/e91619bf4cfa/CAM4-9-6387-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/80510050838e/CAM4-9-6387-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/fdb18a0cd646/CAM4-9-6387-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/963e0db8e3c3/CAM4-9-6387-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/681c2bfbe602/CAM4-9-6387-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da8/7476832/e91619bf4cfa/CAM4-9-6387-g005.jpg

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