HOTAIR promotes proliferation, migration and invasion of esophageal squamous cell carcinoma by regulating MAPK1

Hox transcript antisense intergenic RNA (HOTAIR), a lncRNA expresses from the HOXC locus but represses transcription in more distal HOXD locus and genes on other chromosomes, is overexpressed in esophageal squamous cell carcinoma (ESCC) cell lines and patient samples. HOTAIR could promote ESCC cell proliferation and metastasis, but the underlying mechanism was unclear. The objective of this study was to evaluate the interaction between HOTAIR and mitogen-activated protein kinase 1 (MAPK1) and potential mechanism of HOTAIR in the tumorigenesis and progression of ESCC. In our study, the results of qRT-PCR and western blot showed that expression of HOTAIR and MAPK1 were increased in ESCC patient samples while microRNA (miR)-217 decreased compared with normal tissues, and the expression levels of HOTAIR was correlated with the disease stage. Silencing HOAIR or MAPK1 by shRNA could down-regulate the expression level of each other, but co-silenced with dsRNA endoribonuclease Dicer abolished these effects. These results indicate that HOTAIR might be a ceRNA of MAPK1. Bioinformatics analysis predicts that miR-217 is shared by HOTAIR and MAPK1. MiR-217 mimics could suppress the expression of HOTAIR and MAPK1 in TE1 and KYSE520 while silencing HOTAIR or MAPK1 could increase the expression level of miR-217, indicating the interaction of HOTAIR and MAPK1 was mediated by miR-217. Luciferase reporter assay confirmed this. The cell proliferation, migration and invasion in vitro and tumor formation in vivo of TE1 or KYSE520 were inhibited or decreased after HOTAIR silencing with decreased expression of MAPK1 and activation of its downstream p90RSK. In conclusion, HOTAIR and MAPK1 were up-regulated in ESCC patient samples and HOTAIR could regulate cell proliferation, migration, invasion and tumor formation of ESCC cell line by regulating MAPK1.