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长链非编码RNA转录因子7与多发性骨髓瘤临床特征恶化及预后不良相关,其敲低通过调节miR-203介导的锯齿状蛋白1-Notch1信号通路抑制疾病进展。

lncRNA transcription factor 7 is related to deteriorating clinical features and poor prognosis in multiple myeloma, and its knockdown suppresses disease progression by regulating the miR-203-mediated Jagged1-Notch1 signaling pathway.

作者信息

Liu Haiyan, Shen Yaodong, Xu Ya, Wang Li, Zhang Chenlu, Jiang Yijing, Hong Lemin, Huang Hongming, Liu Hong

机构信息

Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

Department of Hematology, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

出版信息

Oncol Lett. 2021 May;21(5):412. doi: 10.3892/ol.2021.12673. Epub 2021 Mar 22.

Abstract

Multiple myeloma (MM) remains a challenge to treat, and its precise pathogenic mechanisms have not been fully clarified. The present study aimed to evaluate the relation between long non-coding RNA transcription factor 7 (lnc-TCF7) and clinical features, as well as the prognosis of patients with MM, and to determine the effects of lnc-TCF7-knockdown on the regulation (and regulatory mechanisms) of MM progression. lnc-TCF7 expression was detected in the bone marrow plasma cells of 86 patients with MM and 30 healthy controls. In patients with MM, the clinical data were collected, and event-free survival (EFS) and overall survival (OS) analyses were conducted. , lnc-TCF7 expression was detected in MM cell lines and normal bone marrow plasma cells. Using Roswell Park Memorial Institute 8226 cells, functional experiments were conducted following lnc-TCF7 short hairpin (sh)RNA transfection, and compensation experiments were performed after lnc-TCF7 shRNA transfection alone and in combination with a microRNA (miR)-203 inhibitor. lnc-TCF7 expression was increased in patients with MM compared with the healthy controls and was positively related to β-2-microglobulin expression and International Staging System stage, while negatively associated with complete response, EFS and OS. , lnc-TCF7 was upregulated in MM cells compared with normal bone marrow plasma cells, and its knockdown suppressed MM cell proliferation while promoting apoptosis. Compensation experiments showed that miR-203 inhibition promoted MM progression by regulating the Jagged1-Notch1 signaling pathway in lnc-TCF7-knockdown cells. In conclusion, increased lnc-TCF7 expression was related to deteriorating clinical features and prognosis, and lnc-TCF7-knockdown inhibited disease progression by regulating the miR-203-mediated Jagged1-Notch1 signaling pathway activation in MM.

摘要

多发性骨髓瘤(MM)的治疗仍然是一项挑战,其确切的致病机制尚未完全阐明。本研究旨在评估长链非编码RNA转录因子7(lnc-TCF7)与MM患者临床特征及预后之间的关系,并确定lnc-TCF7敲低对MM进展的调控作用(及其调控机制)。检测了86例MM患者和30例健康对照者骨髓浆细胞中的lnc-TCF7表达。收集MM患者的临床数据,并进行无事件生存期(EFS)和总生存期(OS)分析。此外,在MM细胞系和正常骨髓浆细胞中检测了lnc-TCF7表达。使用罗斯威尔帕克纪念研究所8226细胞,在lnc-TCF短链发夹(sh)RNA转染后进行功能实验,并在单独转染lnc-TCF7 shRNA以及与微小RNA(miR)-203抑制剂联合转染后进行补偿实验。与健康对照相比,MM患者lnc-TCF7表达升高,并与β2微球蛋白表达和国际分期系统分期呈正相关,而与完全缓解、EFS和OS呈负相关。此外,与正常骨髓浆细胞相比,MM细胞中lnc-TCF7上调,其敲低可抑制MM细胞增殖,同时促进细胞凋亡。补偿实验表明,miR-203抑制通过调节lnc-TCF7敲低细胞中的Jagged1-Notch1信号通路促进MM进展。总之,lnc-TCF7表达增加与临床特征恶化和预后不良相关,lnc-TCF7敲低通过调节MM中miR-203介导的Jagged1-Notch1信号通路激活来抑制疾病进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cd2/8020383/f65f5ccbe0d4/ol-21-05-12673-g00.jpg

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