HIF1A-AS2 promotes the metabolic reprogramming and progression of colorectal cancer via miR-141-3p/FOXC1 axis.

IF 8.1 1区 生物学 Q1 CELL BIOLOGY Cell Death & Disease Pub Date : 2024-09-03 DOI:10.1038/s41419-024-06958-2
Xinyang Zhong, Yaxian Wang, Xuefeng He, Xinxin He, Zijuan Hu, Huixia Huang, Jiayu Chen, Keji Chen, Ping Wei, Senlin Zhao, Yilin Wang, Hong Zhang, Bo Feng, Dawei Li
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Abstract

lncRNA can regulate tumorigenesis development and distant metastasis of colorectal cancer (CRC). However, the detailed molecular mechanisms are still largely unknown. Using RNA-sequencing data, RT-qPCR, and FISH assay, we found that HIF1A-AS2 was upregulated in CRC tissues and associated with poor prognosis. Functional experiments were performed to determine the roles of HIF1A-AS2 in tumor progression and we found that HIF1A-AS2 can promote the proliferation, metastasis, and aerobic glycolysis of CRC cells. Mechanistically, HIF1A-AS2 can promote FOXC1 expression by sponging miR-141-3p. SP1 can transcriptionally activate HIF1A-AS2. Further, HIF1A-AS2 can be packaged into exosomes and promote the malignant phenotype of recipient tumor cells. Taken together, we discovered that SP1-induced HIF1A-AS2 can promote the metabolic reprogramming and progression of CRC via miR-141-3p/FOXC1 axis. HIF1A-AS2 is a promising diagnostic marker and treatment target in CRC.

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HIF1A-AS2通过miR-141-3p/FOXC1轴促进代谢重编程和结直肠癌的进展。
lncRNA 可调控结直肠癌(CRC)的肿瘤发生、发展和远处转移。然而,其详细的分子机制仍不为人知。利用 RNA 序列数据、RT-qPCR 和 FISH 检测,我们发现 HIF1A-AS2 在 CRC 组织中上调,并与不良预后相关。为了确定 HIF1A-AS2 在肿瘤进展中的作用,我们进行了功能实验,结果发现 HIF1A-AS2 可以促进 CRC 细胞的增殖、转移和有氧糖酵解。从机制上讲,HIF1A-AS2可通过海绵状miR-141-3p促进FOXC1的表达。SP1 可以转录激活 HIF1A-AS2。此外,HIF1A-AS2 还能被包装成外泌体,促进受体肿瘤细胞的恶性表型。综上所述,我们发现SP1诱导的HIF1A-AS2可通过miR-141-3p/FOXC1轴促进代谢重编程和CRC的进展。HIF1A-AS2 是一种很有前景的 CRC 诊断标志物和治疗靶点。
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来源期刊
Cell Death & Disease
Cell Death & Disease CELL BIOLOGY-
CiteScore
15.10
自引率
2.20%
发文量
935
审稿时长
2 months
期刊介绍: Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism
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