Circular RNA circ_0007142 regulates cell proliferation, apoptosis, migration and invasion via miR-455-5p/SGK1 axis in colorectal cancer.
Colorectal cancer (CRC) is a frequently diagnosed cancer worldwide. Accumulating researches suggested that circular RNA 0007142 (circ_0007142) contributed to the progression and initiation of CRC. However, the molecular mechanism of circ_0007142 in CRC needs further research. Levels of circ_0007142, microRNA-455-5p (miR-455-5p), and serum- and glucocorticoid-induced protein kinase 1 (SGK1) were identified by quantitative real-time PCR. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide assay. Flow cytometry assay was used to detect cell apoptosis in SW480 and HCT116 cells. The relative proteins expression was detected by western blot. Cell migration and invasion were evaluated using transwell assay. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays were conducted to determine the relationship between miR-455-5p and circ_0007142 or SGK1. Finally, xenograft tumor model was established to confirm the effect of circ_0007142 on CRC progression in vivo. Circ_0007142 and SGK1 levels were clearly increased, while miR-455-5p level was reduced in CRC tissues and cell lines. Circ_0007142 silencing promoted cell apoptosis and inhibited cell proliferation, migration and invasion, while these effects of circ_0007142 were partially abolished by miR-455-5p inhibitor in CRC cells. Circ_0007142 could sponge miR-455-5p to regulate SGK1 expression. Moreover, the effects of miR-455-5p on cell proliferation, apoptosis, migration and invasion could be partially reversed by SGK1 overexpression. Besides, circ_0007142 knockdown also suppressed the progression of CRC in vivo. Collectively, Circ_0007142/miR-455-5p/SGK1 axis regulated cell proliferation, apoptosis, migration and invasion of CRC cells, providing a probable therapy target for CRC.
Wen T
，Wu H
，Zhang L
，Li K
，Xiao X
，Zhang L
，Zhang Y
... -
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CircCCNB1 silencing acting as a miR-106b-5p sponge inhibited GPM6A expression to promote HCC progression by enhancing DYNC1I1 expression and activating the AKT/ERK signaling pathway.
Background: Circular RNAs (circRNAs), which generally act as microRNA (miRNA) sponges to competitively regulate the downstream target genes of miRNA, play an essential role in cancer biology. However, few studies have been reported on the role of circRNA based competitive endogenous RNA (ceRNA) network in hepatocellular carcinoma (HCC). Herein, we aimed to screen and establish the circRNA/miRNA/mRNA networks related to the prognosis and progression of HCC and further explore the underlying mechanisms of tumorigenesis. Methods: GEO datasets GSE97332, GSE108724, and GSE101728 were utilized to screen the differentially expressed circRNAs (DE-circRNAs), DE-miRNAs, and DEmRNAs between HCC and matched para-carcinoma tissues. After six RNA-RNA predictions and five intersections between DE-RNAs and predicted RNAs, the survival-related RNAs were screened by the ENCORI analysis tool. The ceRNA networks were constructed using Cytoscape software, based on two models of up-regulated circRNA/down-regulated miRNA/up-regulated mRNA and down-regulated circRNA/up-regulated miRNA/down-regulated mRNA. The qRT-PCR assay was utilized for detecting the RNA expression levels in HCC cells and tissues. The apoptosis, Edu, wound healing, and transwell assays were performed to evaluate the effect of miR-106b-5p productions on the proliferation, invasion, and metastasis of HCC cells. In addition, the clone formation, cell cycle, and nude mice xenograft tumor assays were used to investigate the influence of hsa_circ_0001495 (circCCNB1) silencing and overexpression on the proliferation of HCC cells in vitro and in vivo. Furthermore, the mechanism of downstream gene DYNC1I1 and AKT/ERK signaling pathway via the circCCNB1/miR-106b-5p/GPM6A network in regulating the cell cycle was also explored. Results: Twenty DE-circRNAs with a genomic length less than 2000bp, 11 survival-related DE-miRNAs, and 61 survival-related DE-mRNAs were screened out and used to construct five HCC related ceRNA networks. Then, the circCCNB1/miR-106b-5p/GPM6A network was randomly selected for subsequent experimental verification and mechanism exploration at in vitro and in vivo levels. The expression of circCCNB1 and GPM6A were significantly down-regulated in HCC cells and cancer tissues, while miR-106b-5p expression was up-regulated. After transfections, miR-106b-5p mimics notably enhanced the proliferation, invasion, and metastasis of HCC cells, while the opposite was seen with miR-105b-5p inhibitor. In addition, circCCNB1 silencing promoted the clone formation ability, the cell cycle G1-S transition, and the growth of xenograft tumors of HCC cells via GPM6A downregulation. Subsequently, under-expression of GPM6A increased DYNC1I1 expression and activated the phosphorylation of the AKT/ERK pathway to regulate the HCC cell cycle. Conclusions: We demonstrated that circCCNB1 silencing promoted cell proliferation and metastasis of HCC cells by weakening sponging of oncogenic miR-106b-5p to induce GPM6A underexpression. DYNC1I1 gene expression was up-regulated and further led to activation of the AKT/ERK signaling pathway.
Liu YM
，Cao Y
，Zhao PS
，Wu LY
，Lu YM
，Wang YL
，Zhao JF
，Liu XG
... -
《International Journal of Biological Sciences》
ResearchGate
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钛学术
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