Abstract
BackgroundCircular 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.MethodsThe 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.ResultsCircCNIH4 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.ConclusionOur 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.
Highlights
Circular RNAs have been reported to play an important role in tumor progression in various cancer types, including gastric cancer
CircCNIH4 was downregulated in gastric cancer and mainly localized at cytoplasm The expression of circCNIH4 was detected in gastric cancer, and it was found that circCNIH4 level was significantly reduced in gastric cancer tissues compared with normal tissues (Fig. 1a)
The results revealed that Dickkopf 2 (DKK2) and FRZB were remarkably upregulated by circCNIH4 overexpression in both MKN-74 and HGC-27 cells (Fig. 3a, b)
Summary
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. Gastric cancer is one of the most prevalent malignant tumors worldwide, and the morbidity and mortality of gastric cancer are still increasing [1, 2]. Many efforts and improvements have been made in the diagnosis and therapy of gastric. Increasing evidence has indicated that circRNAs play vital roles in the progression of various types of cancer, including gastric cancer [5, 6]. CircHECTD1 contributes to the development of gastric cancer via regulating the miR-1256/USP5 expression
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