title: miR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3K/Akt/mTOR pathway.
abstract: Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that involves the degeneration of keratinocytes. However, the etiology and mechanisms of OLP pathogenesis have not been fully elucidated. In this study, we used keratinocytes HaCaT stimulated with lipopolysaccharide (LPS) to mimic a local OLP immune environment, and investigated the regulatory role of miR-125b in keratinocyte proliferation and apoptosis under OLP conditions. Immunohistochemical analysis and quantitative real-time PCR (qRT-PCR) assay showed that MMP-2 expression was up-regulated and miR-125b expression was down-regulated in both OLP mucosa tissues and LPS-incubated HaCaT cells. Western blot analysis indicated that miR-125b overexpression suppressed LPS-induced MMP-2 expression in HaCaT cells. Molecularly, our results confirmed that MMP-2 is a target gene of miR-125b in HaCaT cells. The effect of miR-125b on cell proliferation was revealed by CCK-8 assay, BrdU assay and cell cycle analysis, which illustrated that miR-125b overexpression impeded LPS-induced HaCaT cell proliferation. Flow cytometry analysis further demonstrated that miR-125b overexpression promoted HaCaT cell apoptosis. Moreover, these effects were involved in PI3K/Akt/mTOR activation, as miR-125b overexpression inhibited LPS-enhanced expression of p-Akt and p-mTOR proteins. Taken together, these data confirm that miR-125b might inhibit keratinocyte proliferation and promote keratinocyte apoptosis in OLP pathogenesis by targeting MMP-2 through PI3K/Akt/mTOR pathway.
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China. Electronic address: jingwangcc@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 Henan, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D017676:Lichen Planus, Oral / Q000201:enzymology* / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C531888:MIRN125 microRNA, human
keywords: Apoptosis; MMP-2; Oral lichen planus; Proliferation; miR-125b