Original ArticleLncRNAAC132217.4, a KLF8-regulated long non-coding RNA, facilitates oral squamous cell carcinoma metastasis by upregulating IGF2 expression

•LncRNA AC132217.4 was upregulated in metastatic OSCC cells.•LncRNA AC132217.4 promoted OSCC cell metastasis via IGF2.•LncRNA AC132217.4 increased IGF2 expression via regulating its stability.•LncRNA AC132217.4 was transcriptionally upregulted by KLF8.•KLF8-AC132217.4-IGF2 axis played an important role in modulating OSCC cell metastasis.

Increasing evidence has revealed the aberrant expression of long non-coding RNAs (lncRNAs) in many cancer types, including oral squamous cell carcinoma (OSCC). However, limited investigations report metastasis-related lncRNAs in OSCC. Herein, we report the identification of dysregulated intergenic lncRNAs in the highly metastatic OSCC cell line, UM-SCC6H. One of the lncRNAs, termed AC132217.4, was remarkably upregulated and promoted cell migration and epithelial-mesenchymal transition (EMT) by upregulating IGF2 expression. Further mechanistic studies revealed that AC132217.4 interacted with the 3′UTR of IGF2 mRNA and increased its stability, leading to increased IGF2 levels. Thereafter, we found that KLF8 binds to the upstream sequence of AC132217.4, activating its expression at the transcriptional level, which accelerated OSCC metastasis via the AC132217.4-IGF2 axis both in vitro and in vivo. We also revealed that the expression level of AC132217.4 was increased in OSCC tissues, and this elevation correlated with KLF8 and IGF2 expression. Thus, our data demonstrate that the KLF8-AC132217.4-IGF2 signalling pathway plays a critical role in OSCC metastasis.