Hypoxia-Regulated lncRNA USP2-AS1 Drives Head and Neck Squamous Cell Carcinoma Progression.
The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1). We ... determined that USP2-AS1 is a direct target of HIF1? and is remarkably elevated in HNSCC compared with matched normal tissues. Patients with a higher level of USP2-AS1 suffered a poor prognosis. Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo. Mechanically, RNA pulldown and LC-MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells. In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR. Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression. Altogether, we found that lncRNA USP2-AS1 functions as a HIF1?-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13.
Mesh Terms:
Cell Line, Tumor, Cell Movement, Chromatography, Liquid, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Humans, Hypoxia, RNA, Antisense, RNA, Long Noncoding, Squamous Cell Carcinoma of Head and Neck, Tandem Mass Spectrometry, Ubiquitin Thiolesterase
Cell Line, Tumor, Cell Movement, Chromatography, Liquid, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms, Humans, Hypoxia, RNA, Antisense, RNA, Long Noncoding, Squamous Cell Carcinoma of Head and Neck, Tandem Mass Spectrometry, Ubiquitin Thiolesterase
Cells
Date: Oct. 28, 2022
PubMed ID: 36359803
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