The circRNA circSCAF8 promotes tumor growth and metastasis of gastric cancer via miR-1293/TIMP1signaling.

IF 4.6 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Gene Therapy Pub Date : 2024-10-27 DOI:10.1038/s41434-024-00496-4

Bin Mei, Jiajie Chen, Yang Peng

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Abstract

SR-like CTD-associated factor 8 (SCAF8) can regulate transcriptional termination, but the function of circSCAF8 remains unclear. In our study, we observed a significant increase in circSCAF8 expression in gastric cancer, particularly in tissues with lymph node metastasis. The Kaplan-Meier curve revealed that high circSCAF8 expression was associated with a low overall survival time in gastric cancer patients. Moreover, circSCAF8 shRNA effectively decreased gastric cancer proliferation, invasion, and migration in vitro. Additionally, using bioluminescence imaging (BLI) technology in vivo, we found that circSCAF8 shRNA viruses inhibited the growth of xenograft tumors and gastric cancer lung metastasis. RNA immunoprecipitation (RIP) and circRNA pulldown assays confirmed the direct binding of circSCAF8 to miR-1293, but circSCAF8 could not regulate the expression of miR-1293 in gastric cancer. Interestingly, circSCAF8 regulated the downstream gene tissue inhibitor of metalloproteinases 1 (TIMP1) of miR-1293, and this observation was further verified in gastric cancer tissues. Moreover, we confirmed that miR-1293 directly suppressed TIMP1 expression. Subsequent rescue experiments revealed that TIMP1 overexpression reversed the impact of circSCAF8 shRNA viruses on gastric cancer. In conclusion, circSCAF8 expression was elevated in gastric cancer, and circSCAF8 shRNA viruses inhibited gastric cancer growth and metastasis by upregulating TIMP1 expression via miR-1293.

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circRNA circSCAF8通过miR-1293/TIMP1信号促进胃癌的生长和转移。

SR 样 CTD 相关因子 8（SCAF8）可调控转录终止，但 circSCAF8 的功能仍不清楚。在我们的研究中，我们观察到 circSCAF8 在胃癌中的表达明显增加，尤其是在淋巴结转移的组织中。Kaplan-Meier 曲线显示，circSCAF8 的高表达与胃癌患者的低总生存时间相关。此外，circSCAF8 shRNA 能有效减少胃癌的体外增殖、侵袭和迁移。此外，我们在体内使用生物发光成像（BLI）技术发现，circSCAF8 shRNA 病毒抑制了异种移植肿瘤的生长和胃癌的肺转移。RNA免疫沉淀（RIP）和circRNA pulldown实验证实了circSCAF8与miR-1293的直接结合，但circSCAF8不能调控胃癌中miR-1293的表达。有趣的是，circSCAF8 可调控 miR-1293 的下游基因组织金属蛋白酶抑制剂 1（TIMP1），这一观察结果在胃癌组织中得到了进一步验证。此外，我们还证实 miR-1293 直接抑制了 TIMP1 的表达。随后的挽救实验显示，TIMP1 的过表达逆转了 circSCAF8 shRNA 病毒对胃癌的影响。总之，circSCAF8在胃癌中表达升高，circSCAF8 shRNA病毒通过miR-1293上调TIMP1的表达，从而抑制胃癌的生长和转移。

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来源期刊

Gene Therapy 医学-生化与分子生物学

CiteScore

9.70

自引率

2.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.