Abstract 996: STAT3 modulates HOTAIR transcription to influence HNSCC growth in vitro and in vivo

Abstract

Abstract Background Squamous cell carcinoma is the most common cancer type of head and neck (HNSCC) with poor prognosis. Signal transducer and activator of transcription 3 (STAT3) activation is involved in HNSCC carcinogenesis as a transcript factor. A new class of transcripts, long noncoding RNAs (lncRNAs), has been recently found to be pervasively transcribed in the genome. HOTAIR, lncRNA Hox transcript antisense intergenic RNA, has been characterized as a novel hall marker to predict poor prognosis in HNSCC. HOTAIR regulates downstream target gene transcription by recruiting polycomb repressive complex 2 (PRC2) to the cell nucleus and triggers triple methylation of H3K27. Methods RNA sequencing, qPCR and CHIP assay were used to determine HOTAIR is a down-stream gene of STAT3. MTT and western blot were employed to examine the regulatory mechanism between STAT3 and HOTAIR in HNSCC cancers in vitro. Additionally, a cell derived xenograft tumor model was used to further validate the anti tumor effect of targeting STAT3/HOTAIR axis in vivo. Results STAT3 depleted HNSCC cell showed decreased HOTAIR expression by qPCR assay. CHIP assay indicated STAT3 bind to the promoter region of HOTAIR encoding gene. Combined inhibition of STAT3 and HOTAIR significantly inhibited cell proliferation, sensitive to cisplatin in HNSCC. Up-regulating HOTAIR partially compensated anti-tumor effect of targeting STAT3 in HNSCC. Conclusion Our data suggested that HOTAIR overexpression is depended on constitutive STAT3 activation in HNSCC and targeting STAT3/HOTAIR axis showed significant therapeutic potential in vitro and in vivo. Citation Format: Xuan Zhou. STAT3 modulates HOTAIR transcription to influence HNSCC growth in vitro and in vivo. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 996.