Research Paper Volume 15, Issue 21 pp 12476—12496
lncRNA HOXC-AS2 promotes the progression of hypopharyngeal cancer by binding to the P62 protein mediating the autophagy process
- 1 Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
- 2 Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, China
- 3 Hubei Provincial Key Lab of Selenium Resources and Bioapplications, Enshi, Hubei 445000, China
- 4 Department of Gastrointestinal Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, China
Received: July 29, 2023 Accepted: October 12, 2023 Published: November 8, 2023
https://doi.org/10.18632/aging.205192How to Cite
Copyright: © 2023 Xiang 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
Hypopharyngeal carcinoma is the most malignant type of head and neck squamous cell carcinoma, and lncRNAs play an important role in its formation and progression. However, the related specific mechanisms are rarely studied. lncRNAs closely associated with hypopharyngeal cancer were examined by lncRNA sequencing for in-depth exploration of the relationship between HOXC-AS2 and hypopharyngeal cancer pathogenesis. The mRNA expression of HOXC-AS2 and related genes was measured by qRT-PCR, and the biological function of HOXC-AS2 in hypopharyngeal carcinoma was demonstrated by gain- and loss-of-function experiments. RNA pulldown, RNA immunoprecipitation (RIP) and gene body truncation experiments and transcriptome sequencing were used to investigate the potential mechanism of HOXC-AS2 and its downstream genes, including P62, NF-KB and HMOX1. Finally, the biological function of HOXC-AS2 was confirmed in animal experiments. HOXC-AS2 and P62 expression was significantly upregulated in hypopharyngeal cancer tissues compared with normal hypopharyngeal tissues, while HMOX1 expression was decreased. Functionally, HOXC-AS2 overexpression can promote the viability, proliferation, migration and invasion of hypopharyngeal cancer cells and facilitate hypopharyngeal cancer progression. It was confirmed that HOXC-AS2 can bind to the P62 protein and activate the NF-KB signaling pathway, thereby affecting HMOX1 expression and regulating autophagy in hypopharyngeal cancer cells, ultimately regulating the formation and progression of hypopharyngeal cancer. In conclusion, our findings suggest that HOXC-AS2 regulates the progression of hypopharyngeal cancer by regulating autophagy and is abnormally highly expressed in hypopharyngeal cancer tissues. HOXC-AS2 may become a new target for the diagnosis and treatment of hypopharyngeal cancer.