JAK1/STAT3通路介导SERPINH1对胶质瘤EMT的影响

IF 4.7 2区 医学 Q2 IMMUNOLOGY
Shuai Wang , Zhiming Sun , Chao Wang , Antian Zhang , Chao Zhang , Shiqiang Hou , Ning Lin , Qun Li
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引用次数: 0

摘要

胶质瘤的特点是细胞增殖迅速,侵袭广泛,预后差。丝氨酸蛋白酶抑制剂H1 (SERPINH1)编码热休克蛋白47,一种胶原特异性分子伴侣,在许多癌症中发挥作用。然而,其在胶质瘤中的确切作用尚不清楚。本研究的目的是探讨SERPINH1在胶质瘤进展中的作用,特别是其对细胞增殖、迁移、侵袭和上皮-间质转化(EMT)的影响。用慢病毒转染胶质瘤细胞系LN229、T98、U251和U87MG,稳定敲低或过表达SERPINH1。通过评估细胞增殖、迁移和侵袭的实验来研究SERPINH1在这些过程中的作用。使用The Cancer Genome Atlas和Chinese Glioma Genome Atlas数据库进行生物信息学分析,以确定与SERPINH1相关的潜在分子途径。Western blotting (WB)检测JAK1/STAT3信号通路和EMT标志物中重要蛋白的表达。用裸鼠进行体内实验,以评估肿瘤的生长和与EMT相关的变化。SERPINH1过表达显著增加胶质瘤细胞的增殖、迁移和侵袭,而敲低则抑制这些活动。生物信息学分析显示,SERPINH1与JAK1/STAT3信号通路和emt相关基因密切相关。WB结果证实,SERPINH1调节JAK1/STAT3的激活,并影响EMT标志物如N-和E-cadherin的水平。JAK1/STAT3激动剂RO8191在SERPINH1敲低组中部分挽救了胶质瘤细胞的行为,而抑制剂STATTIC在SERPINH1过表达组中部分削弱了增强的作用。在体内,SERPINH1过表达加速肿瘤生长和EMT进展,而敲低导致肿瘤大小和EMT标记物表达减少。SERPINH1通过激活JAK1/STAT3信号通路,对胶质瘤的进展、细胞增殖、迁移、侵袭和EMT至关重要。这些结果表明,靶向SERPINH1可能为胶质瘤治疗提供一种有希望的新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The JAK1/STAT3 pathway mediates the effects of SERPINH1 on glioma EMT
Glioma is marked by swift cell proliferation, extensive invasion and poor outcomes. Serine protease inhibitor H1 (SERPINH1) encoding heat shock protein 47, a collagen-specific molecular chaperone, plays a role in a number of cancers. However, its definite role in glioma remains unclear. The aim of the present study was to investigate the role of SERPINH1 in glioma progression, especially its impact on cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). The glioma cell lines LN229, T98, U251 and U87MG were transfected with lentivirus for stable knockdown or overexpression of SERPINH1. Assays assessing cell proliferation, migration and invasion were conducted to investigate the role of SERPINH1 in these processes. Bioinformatic analysis was conducted using The Cancer Genome Atlas and the Chinese Glioma Genome Atlas databases to identify potential molecular pathways associated with SERPINH1. Western blotting (WB) was employed to examine the expression of significant proteins in the JAK1/STAT3 signaling pathway and EMT markers. Nude mice were used for in vivo experiments to evaluate tumor growth and changes related to EMT. Overexpression of SERPINH1 notably increased glioma cell proliferation, migration and invasion, whereas knockdown suppressed these activities. Bioinformatic analyses revealed that SERPINH1 is closely associated with the JAK1/STAT3 signaling pathway and EMT-related genes. WB results confirmed that SERPINH1 regulates the activation of JAK1/STAT3 and influences the levels of EMT markers such as N- and E-cadherin. The JAK1/STAT3 agonist RO8191 partially rescued glioma cell behavior in the SERPINH1 knockdown group, while the inhibitor STATTIC partially weakened the enhanced effects in the SERPINH1 overexpression group. In vivo, SERPINH1 overexpression accelerated tumor growth and EMT progression, while knockdown resulted in a reduction in tumor size and the expression of EMT markers. SERPINH1 is essential for glioma progression, enhancing cell proliferation, migration, invasion and EMT by activating the JAK1/STAT3 signaling pathway. These results indicate that targeting SERPINH1 could provide a promising new approach for glioma therapy.
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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