Long non‐coding RNA HOXC‐AS1 exerts its oncogenic effects in esophageal squamous cell carcinoma by interaction with IGF2BP2 to stabilize SIRT1 expression

Autor: Zhengwu Yang, Junhu Wan, Liwei Ma, Zhuofang Li, Ruotong Yang, Haijun Yang, Junkuo Li, Fuyou Zhou, Liang Ming
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Laboratory Analysis. 37
ISSN: 1098-2825
0887-8013
Popis: Long non-coding RNA HOXC cluster antisense RNA 1 (HOXC-AS1) is a novel lncRNA whose cancer-promoting effect in gastric cancer and nasopharyngeal carcinoma has already been demonstrated. However, its functions in esophageal squamous cell carcinoma (ESCC) remains unknown. LncRNAs can interact with RNA-binding proteins (RBPs) and affect gene expression levels through post-transcriptional regulation. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a widely studied RBP, and sirtuin 1 also known as SIRT1 has been reported to be involved in cancer progression.Establishment of in vivo models, HE and immunohistochemistry staining verified the oncogenic effect of HOXC-AS1. The interaction relationship between HOXC-AS1, IGF2BP2 and SIRT1 was verified by RNA pulldown and RNA immunoprecipitation (RIP) assay. Relative expression and stability changes of genes were detected by qPCR and actinomycin D experiments. Finally, the effect of HOXC-AS1-IGF2BP2-SIRT1 axis on ESCC was verified by rescue experiments.HOXC-AS1 is highly expressed in ESCC cells and plays oncogenic effects in vivo. qPCR showed the positive relationship between HOXC-AS1 and SIRT1 following HOXC-AS1 knockdown or overexpression. RNA-pulldown, mass spectrometry and RIP assay demonstrated that IGF2BP2 is an RBP downstream of HOXC-AS1. Then, RIP and qPCR showed that IGF2BP2 could bind to SIRT1 mRNA and knockdown IGF2BP2 resulted in decreased SIRT1 mRNA level. Finally, a series of rescue assay showed that the HOXC-AS1-IGF2BP2-SIRT1 axis can affect the function of ESCC.LncRNA HOXC-AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.
Databáze: OpenAIRE
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