STRAP 基因敲除抑制非小细胞肺癌的迁移和生长

IF 0.9 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Bulletin of Experimental Biology and Medicine Pub Date : 2024-10-01 Epub Date: 2024-10-26 DOI:10.1007/s10517-024-06267-w
X Chen, C Xu, Y Yang, L Li, R Hong
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引用次数: 0

摘要

丝氨酸-苏氨酸激酶受体相关蛋白(STRAP)通过与多种靶蛋白结合来调节细胞增殖和凋亡,在肿瘤发生发展过程中发挥着重要的调节作用。我们研究了 STRAP 在体内和体外对非小细胞肺癌(NSCLC)的影响,以阐明该蛋白调控作用的可能机制。通过反转录定量 PCR、免疫组化染色和 Western 印迹法测定了 STRAP 在非小细胞肺癌组织和细胞中的水平。在体外实验中,用小干扰 RNA(siRNA)或阴性对照序列转染 A549 和 HCC827 细胞以敲除 STRAP(si-STRAP);分别用划痕法和 Transwell 法检测细胞迁移和侵袭。通过 Western 印迹法测定了 X 连锁凋亡抑制蛋白(XIAP)、caspase-3 和 caspase-9 的表达水平。此外,我们还分析了裸鼠 NSCLC 模型中肿瘤体积的变化。STRAP在NSCLC组织和细胞中高表达,但在转染si-STRAP的A549和HCC827细胞中其表达被显著抑制。敲除 STRAP 能显著抑制 A549 和 HCC827 细胞的迁移和侵袭。它还能明显降低 XIAP 的表达,提高 caspase-3 和 caspase-9 的表达。在移植了 A549 细胞的肿瘤裸鼠中,抑制 STRAP 的表达可延缓肿瘤的生长。总之,这些研究结果表明,STRAP 在 NSCLC 中过表达,而敲除 STRAP 基因可抑制 NSCLC 的生长。
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STRAP Knockdown Inhibits Migration and Growth of Non-Small Cell Lung Cancer.

Serine-threonine kinase receptor-associated protein (STRAP) regulates cell proliferation and apoptosis by binding to many target proteins and plays an important regulatory role in tumor development. We studied the effects of STRAP on non-small cell lung cancer (NSCLC) in vivo and in vitro in order to elucidate possible mechanisms underlying the regulatory effects of this protein. The levels of STRAP in NSCLC tissues and cells were determined by quantitative reverse transcription PCR, immunohistochemical staining, and Western blotting. In in vitro experiments, A549 and HCC827 cells were transfected with small interfering RNA (siRNA) to knockdown STRAP (si-STRAP) or with negative control sequence; cell migration and invasion were detected by scratch and Transwell assays, respectively. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), caspase-3, and caspase-9 were determined by Western blotting. In addition, we analyzed changes of tumor volume in a nude mouse NSCLC model. STRAP was highly expressed in NSCLC tissues and cells, but its expression was significantly suppressed in A549 and HCC827 cells transfected with si-STRAP. STRAP knockdown resulted in a significant inhibition of migration and invasion of A549 and HCC827 cells. It also significantly reduced the expression of XIAP and elevated expression of caspase-3 and caspase-9. In nude mice with tumor originated from transplanted A549 cells, inhibition of STRAP expression retarded the tumor growth. Overall, these findings indicate that STRAP is overexpressed in NSCLC, while knockdown of STRAP gene inhibits the growth of NSCLC.

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来源期刊
Bulletin of Experimental Biology and Medicine
Bulletin of Experimental Biology and Medicine 医学-医学:研究与实验
CiteScore
1.50
自引率
14.30%
发文量
265
审稿时长
2 months
期刊介绍: Bulletin of Experimental Biology and Medicine presents original peer reviewed research papers and brief reports on priority new research results in physiology, biochemistry, biophysics, pharmacology, immunology, microbiology, genetics, oncology, etc. Novel trends in science are covered in new sections of the journal - Biogerontology and Human Ecology - that first appeared in 2005. World scientific interest in stem cells prompted inclusion into Bulletin of Experimental Biology and Medicine a quarterly scientific journal Cell Technologies in Biology and Medicine (a new Russian Academy of Medical Sciences publication since 2005). It publishes only original papers from the leading research institutions on molecular biology of stem and progenitor cells, stem cell as the basis of gene therapy, molecular language of cell-to-cell communication, cytokines, chemokines, growth and other factors, pilot projects on clinical use of stem and progenitor cells. The Russian Volume Year is published in English from April.
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