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.

Details

Title
HIF1A-AS2 promotes the metabolic reprogramming and progression of colorectal cancer via miR-141-3p/FOXC1 axis
Author
Zhong, Xinyang 1 ; Wang, Yaxian 1 ; He, Xuefeng 2 ; He, Xinxin 3 ; Hu, Zijuan 4 ; Huang, Huixia 4 ; Chen, Jiayu 1 ; Chen, Keji 4 ; Wei, Ping 4   VIAFID ORCID Logo  ; Zhao, Senlin 1 ; Wang, Yilin 5 ; Zhang, Hong 6 ; Feng, Bo 7 ; Li, Dawei 1   VIAFID ORCID Logo 

1  Fudan University Shanghai Cancer Center, Department of Colorectal Surgery, Shanghai, China (GRID:grid.452404.3) (ISNI:0000 0004 1808 0942); Shanghai Medical College Fudan University, Department of Oncology, Shanghai, China (GRID:grid.11841.3d) (ISNI:0000 0004 0619 8943) 
2  Zhejiang University School of Medicine, Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, The Second Affiliated Hospital, Hangzhou, China (GRID:grid.412465.0) 
3  Guangxi Medical University Cancer Hospital, Department of Gastrointestinal Surgery, Nanning, China (GRID:grid.256607.0) (ISNI:0000 0004 1798 2653) 
4  Shanghai Medical College Fudan University, Department of Oncology, Shanghai, China (GRID:grid.11841.3d) (ISNI:0000 0004 0619 8943); Fudan University Shanghai Cancer Center, Department of Pathology, Shanghai, China (GRID:grid.452404.3) (ISNI:0000 0004 1808 0942); Fudan University Shanghai Cancer Center, Cancer Institute, Shanghai, China (GRID:grid.452404.3) (ISNI:0000 0004 1808 0942); Fudan University, Institute of Pathology, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
5  Shanghai Medical College Fudan University, Department of Oncology, Shanghai, China (GRID:grid.11841.3d) (ISNI:0000 0004 0619 8943); Fudan University Shanghai Cancer Center, Department of Hepatic Surgery, Shanghai, China (GRID:grid.452404.3) (ISNI:0000 0004 1808 0942) 
6  Shengjing Hospital of China Medical University, Colorectal Tumor Surgery Ward, Department of General Surgery, Shenyang, China (GRID:grid.412636.4) 
7  Shanghai Jiao Tong University School of Medicine, Department of General Surgery, Ruijin Hospital, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293) 
Pages
645
Publication year
2024
Publication date
Sep 2024
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-024-06958-2
ProQuest document ID
3100357228
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.