title: microRNA-130a Promotes Human Keratinocyte Viability and Migration and Inhibits Apoptosis Through Direct Regulation of STK40-Mediated NF-κB Pathway and Indirect Regulation of SOX9-Meditated JNK/MAPK Pathway: A Potential Role in Psoriasis.
abstract: Psoriasis is a chronic inflammatory skin disorder. The aim of this study was to determine a potential role of microRNA (miR)-130a in psoriasis, and underlying mechanism. Expression levels of miR-130a in psoriasis specimens and normal skin tissues were analyzed. MiR-130a mimic, inhibitor, miR-control, small interfering RNA (siRNA) specific serine/threonine kinase 40 (STK40), or sex-determining region Y chromosome-box 9 (SOX9) were transfected to human keratinocyte HaCaT cells, respectively. After transfection, the cell viability, apoptosis, and migration were determined. Luciferase reporter assay, quantitative reverse transcription-polymerase chain reaction, and western blot were performed to explore whether STK40 was a target of miR-130a. The effects of aberrant expressions of miR-130a, STK40, or SOX9 on key proteins of NF-κB and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway were assessed. The miR-130a levels were significantly higher in patients with psoriasis compared to the healthy controls (p < 0.01). Overexpressing miR-130a strikingly promoted HaCaT cell viability and migration and inhibited apoptosis (p < 0.01 or p < 0.05). We confirmed that STK40 was a direct target of miR-130a, and STK40 was involved in miR-130a-induced cell functions. Overexpressing miR-130a significantly upregulated NF-κB p65, SOX9, p-c-Jun, p-JNK, and p-p38MAPK proteins and silencing miR-130a downregulated them. In addition, silencing STK40 alleviated the effects of anti-miR-130a on SOX9 expression. Furthermore, silencing SOX9 also decreased levels of p-c-Jun, p-JNK, and p-p38MAPK proteins. MiR-130a regulates human keratinocyte HaCaT viability, migration and apoptosis might be by direct regulation of STK40-mediated NF-κB pathway and by indirect regulation of SOX9-mediated downstream JNK/MAPK signaling pathway.
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Hongxiao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Liqian
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Leihong
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Zongshan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Fujun
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Dermatology, Linyi People's Hospital , Linyi, China .
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C534864:STK40 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: JNK/MAPK; NF-κB; microRNA-130a; psoriasis; serine/threonine kinase 40; sex-determining region Y chromosome-box 9