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环状 RNA MTO1 通过调控结直肠癌中 Wnt/β-catenin 信号通路抑制细胞增殖和侵袭。

CircMTO1 inhibits cell proliferation and invasion by regulating Wnt/β-catenin signaling pathway in colorectal cancer.

机构信息

Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, Henan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Dec;22(23):8203-8209. doi: 10.26355/eurrev_201812_16513.

Abstract

OBJECTIVE

Circular RNAs (circRNAs) play critical roles in disease incidence. However, the roles of circRNAs in colorectal cancer (CRC) progression remain largely unknown. We explored the expression of circMTO1 in CRC and elucidated the underlying molecular mechanisms.

PATIENTS AND METHODS

Quantitative Real-time-PCR (qRT-PCR) was used to explore circMTO1 expression in CRC tissues and cell lines. The effect of circMTO1 on the biological function of CRC cells was analyzed by Cell Counting Kit-8 (CCK-8) assay, Edu assay, colony formation assay, wound-healing assay and transwell invasion assay. Gene expression and signaling pathway were detected by qRT-PCR and Western blot.

RESULTS

QRT-PCR showed that circMTO1 expression was significantly decreased in CRC tissues and cell lines compared with adjacent non-tumor tissues and human normal colon epithelial cell line (FHC), respectively. Patients with low circMTO1 expression were correlated with advanced TNM stage, lymph node metastasis, and poor overall survival. Function assays demonstrated that circMTO1 inhibition promoted CRC cells proliferation and invasion ability in vitro. In addition, we showed that circMTO1 inhibition could promote CRC progression via activating Wnt/β-catenin signaling pathway.

CONCLUSIONS

We showed that circMTO1 could act as a tumor suppressor affecting the growth and invasion of CRC cells via regulating Wnt/β-catenin signaling pathway, providing a novel potential biomarker and therapeutic target for CRC treatment.

摘要

目的

环状 RNA(circRNAs)在疾病发病机制中发挥着关键作用。然而,circRNAs 在结直肠癌(CRC)进展中的作用在很大程度上仍不清楚。我们探讨了 circMTO1 在 CRC 中的表达,并阐明了其潜在的分子机制。

患者与方法

采用实时定量 PCR(qRT-PCR)检测 CRC 组织和细胞系中 circMTO1 的表达。通过细胞计数试剂盒-8(CCK-8)检测、EdU 检测、集落形成实验、划痕愈合实验和 Transwell 侵袭实验分析 circMTO1 对 CRC 细胞生物学功能的影响。采用 qRT-PCR 和 Western blot 检测基因表达和信号通路。

结果

qRT-PCR 显示,与相邻非肿瘤组织和人正常结肠上皮细胞系(FHC)相比,CRC 组织和细胞系中 circMTO1 的表达明显降低。circMTO1 低表达的患者与较晚的 TNM 分期、淋巴结转移和较差的总生存期相关。功能实验表明,circMTO1 抑制可促进 CRC 细胞在体外的增殖和侵袭能力。此外,我们表明 circMTO1 抑制可通过激活 Wnt/β-catenin 信号通路促进 CRC 进展。

结论

我们表明,circMTO1 可作为一种肿瘤抑制因子,通过调节 Wnt/β-catenin 信号通路影响 CRC 细胞的生长和侵袭,为 CRC 的治疗提供了一种新的潜在的生物标志物和治疗靶点。

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