CircCNIH4 inhibits gastric cancer progression via regulating DKK2 and FRZB expression and Wnt/β-catenin pathway.

IF 1.9 3区生物学 Q2 BIOLOGY

Journal of Biological Research-Thessaloniki Pub Date : 2021-08-07 DOI:10.1186/s40709-021-00140-x

Qi Shi, Chuanwen Zhou, Rui Xie, Miaomiao Li, Peng Shen, Yining Lu, Shijie Ma

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引用次数: 4

Abstract

Background: Circular RNAs (circRNAs) have been reported to play an important role in tumor progression in various cancer types, including gastric cancer. The aim of this study was to investigate the role of circCNIH4 (hsa_circ_0000190) in gastric cancer and the underlying mechanism.

Methods: The expression levels of circCNIH4 and Wnt antagonist genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of β-catenin, Ki67, Dickkopf 2 (DKK2) and Frizzled related protein (FRZB) were measured by western blot. Ectopic overexpression or knockdown of circCNIH4, proliferation, apoptosis, migration and invasion by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry and transwell assay in vitro, and in vivo experiment, were employed to assess the role of circCNIH4 in gastric cancer.

Results: CircCNIH4 was downregulated in gastric cancer tissues and cells. Overexpression of circCNIH4 inhibited gastric cancer cell proliferation, migration and invasion and promoted apoptosis by inactivating Wnt/β-catenin pathway in vitro. CircCNIH4 induced the expression of DKK2 and FRZB in gastric cancer cells. Moreover, silencing of DKK2 or FRZB reversed circCNIH4 overexpression-mediated effects on gastric cancer cells. Additionally, circCNIH4 suppressed tumor growth via regulating DKK2 and FRZB expression in gastric cancer in vivo.

Conclusion: Our study demonstrated that circCNIH4 played a tumor-inhibiting role through upregulating DKK2 and FRZB expression and suppressing Wnt/β-catenin pathway in gastric cancer, which might provide a potential biomarker for the diagnosis and treatment of gastric cancer.

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CircCNIH4通过调节DKK2和FRZB表达以及Wnt/β-catenin通路抑制胃癌进展。

背景:环状rna (circRNAs)已被报道在包括胃癌在内的各种癌症类型的肿瘤进展中发挥重要作用。本研究的目的是探讨circCNIH4 (hsa_circ_0000190)在胃癌中的作用及其潜在机制。方法:采用实时荧光定量聚合酶链式反应(qRT-PCR)检测circCNIH4和Wnt拮抗剂基因的表达水平。western blot检测β-catenin、Ki67、dickkopf2 (DKK2)和frzledrelated protein (FRZB)蛋白水平。采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2- h -溴化四氮唑(MTT)、体外流式细胞术、transwell实验和体内实验，探讨了circCNIH4异位过表达或下调、增殖、凋亡、迁移和侵袭作用。结果:CircCNIH4在胃癌组织和细胞中表达下调。体外实验表明，过表达circCNIH4通过灭活Wnt/β-catenin通路，抑制胃癌细胞增殖、迁移和侵袭，促进凋亡。CircCNIH4诱导胃癌细胞中DKK2和FRZB的表达。此外，DKK2或FRZB的沉默逆转了circCNIH4过表达介导的胃癌细胞效应。此外，circCNIH4在体内通过调节DKK2和FRZB在胃癌中的表达抑制肿瘤生长。结论:我们的研究表明，circCNIH4通过上调DKK2和FRZB的表达，抑制Wnt/β-catenin通路在胃癌中发挥肿瘤抑制作用，可能为胃癌的诊断和治疗提供潜在的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Research-Thessaloniki 生物-生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Biological Research-Thessaloniki is a peer-reviewed, open access, international journal that publishes articles providing novel insights into the major fields of biology. Topics covered in Journal of Biological Research-Thessaloniki include, but are not limited to: molecular biology, cytology, genetics, evolutionary biology, morphology, development and differentiation, taxonomy, bioinformatics, physiology, marine biology, behaviour, ecology and conservation.