LncRNA THRIL is involved in the proliferation, migration, and invasion of rheumatoid fibroblast-like synoviocytes.
LncRNA THRIL is involved in the proliferation, migration, and invasion of rheumatoid fibroblast-like synoviocytes.
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LncRNA THRIL参与类风湿成纤维样滑膜细胞的增殖、迁移和侵袭
DOI：
10.21037/atm-21-1362
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发表时间：
2021-09
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Zou Y;Shen C;Shen T;Wang J;Zhang X;Zhang Q;Sun R;Dai L;Xu H
背景成纤维细胞样滑膜细胞（FLS）是类风湿性关节炎（RA）关节损伤的重要参与者，它可以迁移并直接侵入软骨和骨。然而，RA FLS异常激活的详细机制仍不清楚。一些研究试图探索长链非编码RNA（lncRNA）与RA病理学之间的关系;然而，lncRNA在RA中的作用尚不清楚。本研究旨在探讨肿瘤坏死因子-α（TNF-α）和异质性核核糖核蛋白L相关免疫调节lincRNA（THRIL）在类风湿关节炎FLS迁移和侵袭中的作用。方法采用靶向THRIL的小干扰RNA或过表达THRIL的慢病毒，敲低或过表达THRIL。采用定量逆转录聚合酶链反应（PCR）检测RNA表达。采用5-乙炔基-2 '-脱氧尿苷（EdU）掺入法测定RA FLS的增殖率。用transwell小室检测迁移和侵袭。使用人细胞周期实时PCR阵列和人细胞运动性实时PCR阵列鉴定下游靶标。结果RA FLS中THRIL的表达明显低于健康对照组（HC）。THRIL主要定位于细胞核。THRIL的敲低增加了RA FLS的增殖、迁移和侵袭。相反，THRIL过表达具有相反的效果。THRIL敲低增加了白细胞介素-1 β（IL-1β）触发的基质金属蛋白酶（MMP）-1，MMP-3和MMP-13的表达。THRIL过表达导致MMP-13表达对IL-1β刺激的响应显著降低。此外，我们观察到，细胞周期蛋白依赖性激酶1（CDK 1）和G2和S期表达-1（GTSE 1）的表达水平，这两者都与细胞的流动性和增殖，下调与THRIL过表达。结论lncRNA THRIL表达降低可抑制RA FLS的增殖、迁移和侵袭，提示lncRNA THRIL可能是RA治疗的潜在靶点。
Background Fibroblast-like synoviocytes (FLSs), which can migrate and directly invade the cartilage and the bone, are crucial players in joint damage in rheumatoid arthritis (RA). Nevertheless, the detailed mechanisms underlying the aberrant activation of RA FLSs remain unclear. Several studies have attempted to explore the relationship between long non-coding RNAs (lncRNAs) and RA pathology; however, the role of lncRNAs in RA is unknown. The present study aimed to determine the functions of tumor necrosis factor-α and heterogeneous nuclear ribonucleoprotein L-related immunoregulatory lincRNA (THRIL) in RA FLSs migration and invasion. Methods Small interfering RNA targeting THRIL or lentivirus overexpressing THRIL was used to knockdown or overexpress THRIL. Quantitative reverse transcription polymerase chain reaction (PCR) was employed for the detection of RNA expression. The proliferation rate of RA FLSs was measured using a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Migration and invasion were detected using a transwell chamber. Downstream targets were identified using a human cell cycle real-time PCR array and a human cell motility real-time PCR array. Results A significant decrease in THRIL expression was found in RA FLSs compared with cells from healthy control (HC)patients. THRIL is mainly localized in the nucleus. Knockdown of THRIL increased the proliferation, migration, and invasion of RA FLSs. In contrast, THRIL overexpression had the opposite effect. THRIL knockdown increased interleukin-1β (IL-1β)-triggered expression of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13. THRIL overexpression led to a significant decrease in MMP-13 expression in response to stimulation with IL-1β. Furthermore, we observed that the expression levels of cyclin-dependent kinase 1 (CDK1) and G2 and S phase-expressed-1 (GTSE1), both of which are associated with cellular mobility and proliferation, were downregulated with THRIL overexpression. Conclusions Reduced expression of lncRNA THRIL represses the proliferation, migration, and invasion of RA FLSs, suggesting that lncRNA THRIL might be a potential target for RA therapy.
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影响因子：
16.6
作者：
Kelly, Joanna R.;Martini, Silvia;Soliman, Tanya N.
通讯作者：
Soliman, Tanya N.
影响因子：
64.8
作者：
Cuylen S;Blaukopf C;Politi AZ;Müller-Reichert T;Neumann B;Poser I;Ellenberg J;Hyman AA;Gerlich DW
通讯作者：
Gerlich DW
影响因子：
5.1
作者：
Liang, Yongjian;Li, He;Ding, Chao
通讯作者：
Ding, Chao
沉默GTSE-1表达抑制肝癌细胞增殖和侵袭
影响因子：
6.1
作者：
Guo L;Zhang S;Zhang B;Chen W;Li X;Zhang W;Zhou C;Zhang J;Ren N;Ye Q
通讯作者：
Ye Q
类风湿关节炎中成纤维细胞样的滑膜细胞的转化；从朋友到敌人。
DOI：
10.1186/s13317-020-00145-x
发表时间：
2021-02-05
期刊：
Auto- immunity highlights
影响因子：
--
作者：
Mousavi MJ;Karami J;Aslani S;Tahmasebi MN;Vaziri AS;Jamshidi A;Farhadi E;Mahmoudi M
通讯作者：
Mahmoudi M