Long Non-coding RNA HOTAIR Is Targeted and Regulated by miR-141 in Human Cancer Cells

Background: Silencing of long non-coding RNA (lncRNA) by microRNA (miRNA) has only been recently observed. Results: miR-141 binds to HOTAIR and suppresses its oncogenic function in Ago2 (Argounaute2). Conclusion: miR-141 targets and silences HOTAIR in an Ago2-dependent manner in cancer cells. Significance: Our results suggest that regulation of lncRNA expression by miRNA plays essential roles in gene expression and cellular functions. HOTAIR is a long non-coding RNA that interacts with the polycomb repressive complex and suppresses its target genes. HOTAIR has also been demonstrated to promote malignancy. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition process, and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. We found that HOTAIR expression is inversely correlated to miR-141 expression in renal carcinoma cells. HOTAIR promotes malignancy, including proliferation and invasion, whereas miR-141 suppresses malignancy in human cancer cells. miR-141 binds to HOTAIR in a sequence-specific manner and suppresses HOTAIR expression and functions, including proliferation and invasion. Both HOTAIR and miR-141 were associated with the immunoprecipitated Ago2 (Argonaute2) complex, and the Ago2 complex cleaved HOTAIR in the presence of miR-141. These results demonstrate that HOTAIR is suppressed by miR-141 in an Ago2-dependent manner.