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Circ_SMAD4 promotes gastric carcinogenesis by activating wnt/β‐catenin pathway
Cell Proliferation ( IF 5.9 ) Pub Date : 2021-01-17 , DOI: 10.1111/cpr.12981
Liyan Wang 1 , Bin Li 1 , Xiaoyuan Yi 1 , Xuhua Xiao 1 , Qinghua Zheng 1 , Lei Ma 1
Affiliation  

OBJECTIVES Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC). METHODS Gene expression was detected by qRT-PCR or Western blot. Survival curves were generated via Kaplan-Meier method. In vitro and in vivo assays were used to investigate the impact of circ_SMAD4 on GC cell growth and tumorigenesis. Agarose gel electrophoresis assay, RNase R treatment and Sanger sequencing were utilized for confirming the circular structure of circ_SMAD4. Relationship between molecules was monitored by a series of mechanical experiments, as needed. RESULTS Circ_SMAD4 expression was potentiated in GC. Circ_SMAD4 depletion impeded GC cell growth in vitro and restrained tumorigenesis in vivo. Mechanically, nuclear circ_SMAD4 recruited TCF4 to facilitate CTNNB1 transcription, while cytoplasmic circ_SMAD4 sequestered miR-1276 to prevent the silence of CTNNB1 mRNA, leading to activation of Wnt/β-catenin pathway. Rescue experiments validated that circ_SMAD4 depended on miR-1276/TCF4-regulated CTNNB1 to elicit accelerating effects on GC cell growth. CONCLUSION Circ_SMAD4 facilitated GC tumorigenesis by activating CTNNB1-dependent Wnt/β-catenin pathway. Hopefully, the findings could provide new clues for improving GC prognosis and treatment.

中文翻译:

Circ_SMAD4通过激活wnt/β-catenin通路促进胃癌发生

目的 环状 RNA (circRNA) 是肿瘤进展的重要参与者。本研究的重点是研究一种新型功能 circRNA 在胃癌 (GC) 中的作用机制。方法通过qRT-PCR或Western blot检测基因表达。通过 Kaplan-Meier 方法生成生存曲线。体外和体内试验用于研究 circ_SMAD4 对 GC 细胞生长和肿瘤发生的影响。琼脂糖凝胶电泳分析、RNase R 处理和 Sanger 测序用于确认 circ_SMAD4 的环状结构。根据需要,通过一系列机械实验监测分子之间的关系。结果 Circ_SMAD4 表达在 GC 中得到增强。Circ_SMAD4 耗竭阻碍了体外 GC 细胞的生长并抑制了体内肿瘤的发生。机械地,核 circ_SMAD4 募集 TCF4 以促进 CTNNB1 转录,而细胞质 circ_SMAD4 隔离 miR-1276 以防止 CTNNB1 mRNA 的沉默,从而激活 Wnt/β-catenin 通路。救援实验证实,circ_SMAD4 依赖于 miR-1276/TCF4 调节的 CTNNB1 来引发对 GC 细胞生长的加速作用。结论 Circ_SMAD4 通过激活 CTNNB1 依赖的 Wnt/β-catenin 通路促进 GC 肿瘤发生。希望这些发现可以为改善胃癌预后和治疗提供新的线索。结论 Circ_SMAD4 通过激活 CTNNB1 依赖的 Wnt/β-catenin 通路促进 GC 肿瘤发生。希望这些发现可以为改善胃癌预后和治疗提供新的线索。结论 Circ_SMAD4 通过激活 CTNNB1 依赖的 Wnt/β-catenin 通路促进 GC 肿瘤发生。希望这些发现可以为改善胃癌预后和治疗提供新的线索。
更新日期:2021-01-17
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