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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: LncRNA HOXC‐AS1 acts as an oncogenic role in ESCC, which impacts ESCC progression by interaction with IGF2BP2 to stabilize SIRT1 expression.