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The reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a membrane-anchored glycoprotein, negatively regulates various membrane proteins involved in the tissue governing extracellular matrix (ECM) remodeling such as metalloproteases (MMPs) and the sheddases ADAM10 and ADAM17. The significance of the present review is to summarize the current understanding of the pathophysiological role of RECK, a newly discovered signaling pathway associated with different liver injuries. Specifically, this review analyzes published data on the downregulation of RECK expression in hepatic ischemia/reperfusion (I/R) injury, liver-related cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), as well as in the progression of nonalcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). In addition, this review discusses the regulation of RECK by inducers, such as FXR agonists. The RECK protein has also been suggested as a potential diagnostic and prognostic marker for liver injury or as a biomarker with predictive value for drug treatment efficacy.

Objective To investigate the impact of miR-181c on migration and angiogenesis of lung cancer cells. Methods The Oncomine platform, UALCAN was used to analyze the differential expression of miR-181c and reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in lung cancer obtained from the Cancer Genome Atlas (TCGA) database. The targeting relationship between miR-181c on RECK gene was predicted using Targetscan software. miR-181c mimic, inhibitor and negative control were introduced into A549 cells respectively. After transfection, the real-time quantitative PCR was used to detect the relative expressions of miR-181c and RECK mRNA, and Western blot analysis was used to detect the expression levels of RECK, matrix metalloproteinase 2 (MMP2) and MMP9 proteins. Transwell TM assay was performed to analyze the cell migration ability. The secretion of vascular endothelial growth factor (VEGF)-A in the cell culture supernatant was analyzed by using ELISA. Human umbilical vein endothelial cells (HUVECs) were treated with the culture supernatant, then in vitro tubule formation assay was carried out to evaluate the angiogenesis ability. The targeting correlation between miR-181c and RECK was validated by double luciferase reporter gene assay. Results UALCAN analysis displayed that the expression of miR-181c was significantly higher and RECK expression was significantly lower in lung cancer tissues compared to that in normal tissues. Targetscan prediction showed that there was a miR-181c binding site in the 3'-untranslated region (3' UTR) of RECK gene. miR-181c could downregulate the expression of RECK, increase the expressions of MMP2 and MMP9, and promote the A549 cell migration. ELISA and tubule formation assay showed that miR-181c could induce the secretion of VEGF-A in A549 cells and enhance the ability of HUVECs differentiae into tubules. The double luciferase reporter gene assay confirmed that RECK was the direct regulation target of miR-181c. Conclusion miR-181c promotes the migration and angiogenesis of human A549 cells by directly targeting RECK.