Mechanism of miR-340–5p in laryngeal cancer cell proliferation and invasion through the lncRNA NEAT1/MMP11 axis

Abstract

ObjectivesLaryngeal cancer (LC), with a relatively rare diagnosis, is a primary malignancy originating from laryngeal mucosa. This study investigated the mechanisms of microRNA (miR)- 340–5p in LC cell proliferation and invasion. MethodsThe expression patterns of miR-340–5p, long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1), and matrix metallopeptidase 11 (MMP11) in LC cells, tissues, and para-carcinoma tissues, and human bronchial epithelial cells (HBEC) were examined via RT-qPCR. The effects of elevating or silencing miR-340–5p on LC cell proliferation and invasion were examined. The subcellular localization of lncRNA NEAT1 was determined. The binding relations among miR-340–5p, lncRNA NEAT1, and MMP11 were verified. Functional rescue experiments were designed to verify the functions of lncRNA NEAT1 and MMP11 on LC cell proliferation and invasion. Nude-mouse tumor models were established to assess the role of miR-340–5p in LC in vivo. ResultsmiR-340–5p was under-expressed in LC, and miR-340–5p overexpression repressed LC cell proliferation and invasion. Mechanically, miR-340–5p decreased lncRNA NEAT1 stability via directly binding to lncRNA NEAT1 and thus declined lncRNA NEAT1 expression in LC cells, while lncRNA NEAT1 accelerated MMP11 transcription via binding to heat shock factor 1 (HSF1). Overexpression of lncRNA NEAT1 or MMP11 reversed the repression of miR-340–5p overexpression on LC cell proliferation and invasion. In vivo, miR-340–5p overexpression repressed the tumor growth. ConclusionmiR-340–5p overexpression reduced lncRNA NEAT1 stability via binding to lncRNA NEAT1, which declined lncRNA NEAT1 expression and reduced the binding of lncRNA NEAT1 to HSF1 to further inhibit MMP11 transcription, thus repressing LC cell proliferation and invasion.