Hesperidin administration suppresses the proliferation of lung cancer cells by promoting apoptosis via targeting the miR-132/ZEB2 signalling pathway

This aim of the present study was to identify the relationship between hesperidin and microRNA (miR)-132, and to study the role of hesperidin and miR-132 in the pathogenesis of non-small cell lung cancer (NSCLC). Computational analysis and luciferase assays were performed to identify the target of miR-132. Subsequently, reverse transcription-quantitative PCR and western blot assays were used to detect the effect of miR-132 and hesperidin on the expression of haematological and neurological expressed 1 (HN1) and zinc finger E-box binding homeobox 2 (ZEB2). Finally, MTT assays and flow cytometry analysis were used to investigate the effect of hesperidin on cell proliferation and apoptosis. ZEB2 was identified as a target gene of miR-132, and transfection with miR-132 mimic reduced the luciferase activity of the wild-type ZEB2 3′-untranslated region (3′-UTR) but not that of the mutant ZEB2 3′-UTR. By contrast, neither transfection with miR-132 mimic nor hesperidin treatment affected HN1 expression. Furthermore, hesperidin evidently inhibited cell proliferation and promoted apoptosis in a dose-dependent manner. Furthermore, the tumour volume in rats transplanted with NSCLC cells and treated with hesperidin was notably smaller compared with that in rats transplanted with NSCLC cells alone, while treatment with hesperidin significantly reduced the colony formation efficiency of NSCLC cells by increasing miR-132 expression and decreasing ZEB2 expression. To the best of our knowledge, the present study demonstrated for the first time that the administration of hesperidin decreased the expression of ZEB2 by upregulating the expression of miR-132, which in turn promoted apoptosis and inhibited the proliferation of NSCLC cells.