Research Paper Volume 16, Issue 9 pp 7752—7773
Long non-coding RNA HOTAIR: from pan-cancer analysis to colorectal cancer-related uridine metabolism
- 1 Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- 2 Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
Received: September 26, 2023 Accepted: March 29, 2024 Published: May 1, 2024
https://doi.org/10.18632/aging.205781How to Cite
Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. lncRNA HOTAIR has been reported to play an oncogenic role in many human cancers. Its specific regulatory role is still elusive. And it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. We comprehensively investigated the effect of HOTAIR expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases like The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). Bioinformatics data indicated that HOTAIR was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer, especially in colorectal cancer (CRC). Subsequently, this study further clarified the utility of HOTAIR that downregulation of its expression could result in reduced proliferation and invasion of CRC cells. Mechanistically, HOTAIR upregulated the metabolic enzymes UPP1 by recruiting histone methyltransferase EZH2, thereby increasing the tumor progression. Our results highlight the essential role of HOTAIR in pan-cancer and uridine bypass, suggesting that the HOTAIR/EZH2/UPP1 axis might be a novel target for overcoming CRC. We anticipate that the role of HOTAIR in metabolism could be important in the context of CRC and even exploited for therapeutic purposes.
Abbreviations
lncRNAs: long non-coding RNAs; TIMER: Tumor Immune Estimation Resource; GEPIA: Gene Expression Profiling Interactive Analysis; TCGA: The Cancer Genome Atlas; GEO: The Gene Expression Omnibus; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: gene ontology; GTEx: Genotype-Tissue Expression; OS: overall survival; DFS: disease-free survival; CPTAC: Clinical Proteomics Tumor Analysis Consortium; FBS: fetal bovine serum; BRCA: breast invasive carcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KIRP: kidney renal clear cell carcinoma; KIRC: kidney renal papillary cell carcinoma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; PCPG: pheochromocytoma and paraganglioma; READ: rectum adenocarcinoma; STAD: stomach adenocarcinoma; THCA: thyroid carcinoma; KICH: kidney chromophobe; MESO: mesothelioma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; PAAD: pancreatic adenocarcinoma; ROC: receiver operating characteristic; AUC: area under the curve; PRC2: polycomb repressive complex 2; HOXD: homeobox gene D cluster; PDL1: programmed cell death-ligand 1.