KCNQ1OT1 通过调控 miR-183-3p/GAB1 促进银屑病角质形成细胞的增殖和迁移。
KCNQ1OT1 promotes the proliferation and migration of psoriatic keratinocytes by regulating miR-183-3p/GAB1.
机构信息
Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China;
Department of Dermatology, Affiliated Hospital of North Sichuan Medical College, Nanchong City 637000, Sichuan Province, China.
出版信息
Allergol Immunopathol (Madr). 2021 Sep 1;49(5):125-130. doi: 10.15586/aei.v49i5.480. eCollection 2021.
BACKGROUND
Differentially expressed long non-coding RNAs (lncRNA) have been reported to be involved in the proliferation and migration of keratinocyte. Potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) was implicated in the pathogenesis of various diseases, including cancer, sepsis, diabetic cardiomyopathy, and atherosclerosis. In this study, the influence of KCNQ1OT1 on the proliferation and migration of psoriatic keratinocytes was explained.
METHODS
Cultured human keratinocyte cell line (HaCaT) was incubated with tumor necrosis factor-α (TNF-α). Cell viability and migration were assessed by MTT assay and wound healing, respectively. Target miRNA of KCNQ1OT1 was identified by luciferase activity and RNA immunoprecipitation (RIP) assays.
RESULTS
KCNQ1OT1 was up-regulated in TNF-α-treated HaCaT cell line, and knockdown of KCNQ1OT1 reduced viability and suppressed the migration of TNF-α-treated HaCaT cell line. KCNQ1OT1 was bound to microRNA-183-3p (miR-183-3p) and negatively regulated its expression. Over-expression of growth factor receptor binding 2-associated binding protein 1 (GAB1) counteracted with the suppressive effects of KCNQ1OT1-induced silence on the viability and migration of TNF-α-treated HaCaT cells.
CONCLUSION
KCNQ1OT1 silence suppressed the proliferation and migration of TNF-α-treated HaCaT cells through regulation of miR-183-3p/GAB1.
背景
差异表达的长链非编码 RNA（lncRNA）已被报道参与角质形成细胞的增殖和迁移。钾电压门控通道亚家族 Q 成员 1 重叠转录本 1（KCNQ1OT1）与多种疾病的发病机制有关，包括癌症、脓毒症、糖尿病心肌病和动脉粥样硬化。在这项研究中，解释了 KCNQ1OT1 对银屑病角质形成细胞增殖和迁移的影响。
方法
培养人角质形成细胞系（HaCaT）并用肿瘤坏死因子-α（TNF-α）孵育。通过 MTT 测定和划痕愈合分别评估细胞活力和迁移。通过荧光素酶活性和 RNA 免疫沉淀（RIP）测定鉴定 KCNQ1OT1 的靶 miRNA。
结果
KCNQ1OT1 在 TNF-α 处理的 HaCaT 细胞系中上调，并且 KCNQ1OT1 的敲低降低了 TNF-α 处理的 HaCaT 细胞系的活力并抑制了其迁移。KCNQ1OT1 与 microRNA-183-3p（miR-183-3p）结合并负调控其表达。生长因子受体结合 2 相关结合蛋白 1（GAB1）的过表达抵消了 KCNQ1OT1 诱导沉默对 TNF-α 处理的 HaCaT 细胞活力和迁移的抑制作用。
结论
KCNQ1OT1 沉默通过调节 miR-183-3p/GAB1 抑制 TNF-α 处理的 HaCaT 细胞的增殖和迁移。
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