LncRNAAC132217.4, a KLF8-regulated long non-coding RNA, facilitates oral squamous cell carcinoma metastasis by upregulating IGF2 expression

  • Cancer Lett. 2017 Oct 28;407:45-56. doi: 10.1016/j.canlet.2017.08.007.
Xiaojie Li  1 ,  Changhong Ma  2 ,  Li Zhang  3 ,  Na Li  4 ,  Xiaohong Zhang  1 ,  Jianya He  1 ,  Ruiping He  1 ,  Miaomiao Shao  1 ,  Junling Wang  1 ,  Lan Kang  5 ,  Chuanchun Han  6
Affiliations
  • 1. Institute of Cancer Stem Cell & College of Stomatology, Dalian Medical University, Dalian 116044, China.
  • 2. Department of Otorhinolaryngology, The First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
  • 3. Laboratory of Pathogenic Biology, College of Basic Medical Science of Dalian Medical University, Dalian 116044, China.
  • 4. Pathology Department of College of Basic Medical Science, Dalian Medical University, Dalian 116044, China.
  • 5. Institute of Cancer Stem Cell & College of Stomatology, Dalian Medical University, Dalian 116044, China. Electronic address: [email protected].
  • 6. Institute of Cancer Stem Cell & College of Stomatology, Dalian Medical University, Dalian 116044, China. Electronic address: [email protected].
PMID: 28823965 DOI: 10.1016/j.canlet.2017.08.007
Abstract

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.

Keywords
Cell meatastasis; IGF2; KLF8; LncRNAs; Oral squamous cell carcinoma.