Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis

Zhang, Xiaoyu; Xu, Yingying; Yamagata, Kenji; Hu, Jian; Zhang, Lianbo; Wang, Jianfeng; Tian, Jiayi; Chen, Wanying

doi:10.1186/s12935-020-01178-y

Cited by 28 publications

(19 citation statements)

References 37 publications

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“…However, examination of TCGA colorectal cancer datasets via cBioPortal revealed rare amplification of CREB5, suggesting that overexpression of CREB5 is controlled at transcriptional and post-transcriptional levels. CREB5 has been shown to be a downstream target of LncRNA SNHG5/miR-132-3p [14] and circular RNA circVAPA/miR-125a [26]. In addition, FZD3 inhibits transcriptional networks controlled by CREB5 [25].…”

Section: Discussionmentioning

confidence: 99%

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

Wang

Qiu

Liu

et al. 2020

J Exp Clin Cancer Res

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Background: cAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear. Methods: Real-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC. Results: We found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling. Conclusion: Our study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.

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Section: Discussionmentioning

confidence: 99%

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

Wang

Qiu

Liu

et al. 2020

J Exp Clin Cancer Res

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“…The doublecortin-like kinase 1 (DCLK1) [ 33 ] and lncRNA ANRIL [ 34 ] have been found to be negative regulators of let-7a-5p expression in CRC cell lines. Expression of miR-125a-5p is strongly influenced by hypermethylation in CRC tumours [ 23 ], and it has been shown to be sequestered by lncRNA HOXA11-AS [ 35 ] and circRNA VAPA ( Supplementary Table S5 ) [ 36 ]. miR-125b-5p/3p is subjected to complex regulation, including via the transcription factors peroxisome-proliferator-activated receptor gamma (PPARG), nuclear factor kappa B subunit 1 (NFKB1), tumour protein p53 (p53), MYC proto-oncogene, bHLH transcription factor (MYC), caudal type homeobox 2 (CDX2), lncRNA NEAT1, MEG3, UCA1 and MALAT1 [ 37 ], and by methylation [ 23 ].…”

Section: Mirna Clusters Down-regulated In Human Crcmentioning

confidence: 99%

“…miR-125a-5p also executes its functions via targeting genes coding for peptidyl arginine deiminase 2 ( PADI2 ) involved in the promotion of metastasis [ 35 ] and pro-angiogenic vascular endothelial growth factor A ( VEGFA ) [ 69 ]. miR-125a-5p also inhibits cell proliferation and migration by targeting SMAD-specific E3 ubiquitin protein ligase 1 ( SMURF1 ) [ 70 ], phospholipid:diacylglycerol acyltransferase, called tafazzin ( TAZ ) [ 71 ] and cAMP-responsive element-binding protein 5 ( CREB5 ) [ 36 ]. Overexpression of miR-125a-3p inhibits cell proliferation and migration through targeting fucosyltransferases 5 and 6 ( FUT5 and FUT6 , respectively) [ 72 ].…”

Section: Mirna Clusters Down-regulated In Human Crcmentioning

confidence: 99%

miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

Pidíková

Reis

Herichová

2020

IJMS

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Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miRNAs “sponging” by long non-coding RNAs (ncRNAs). Both types of miRNA regulation strongly influence their function. We focused on clusters of miRNAs found to be down-regulated in CRC, containing miR-1, let-7, miR-15, miR-16, miR-99, miR-100, miR-125, miR-133, miR-143, miR-145, miR-192, miR-194, miR-195, miR-206, miR-215, miR-302, miR-367 and miR-497 and analysed their genome position, regulation and functions. Only evidence provided with the use of CRC in vivo and/or in vitro models was taken into consideration. Comprehensive research revealed that down-regulated miRNA clusters in CRC are mostly located in a gene intron and, in a majority of cases, miRNA clusters possess cluster-specific transcriptional regulation. For all selected clusters, regulation mediated by long ncRNA was experimentally demonstrated in CRC, at least in one cluster member. Oncostatic functions were predominantly linked with the reviewed miRNAs, and their high expression was usually associated with better survival. These findings implicate the potential of down-regulated clusters in CRC to become promising multi-targets for therapeutic manipulation.

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“… 29 CircVAPA contributed to CRC cell growth and glycolysis by directly combining with miR-125a to release CREB5 . 30 In this research, we determined that silenced circ-PRKDC suppressed CRC cell proliferation, migration and invasion, and triggered apoptosis. Subsequently, we selected miR-198 as a possible target for circ-PRKDC based on bioinformatics analysis.…”

Section: Discussionmentioning

confidence: 96%

<p>Circ-PRKDC Facilitates the Progression of Colorectal Cancer Through miR-198/DDR1 Regulatory Axis</p>

Wang¹,

Li²,

Zhu³

et al. 2020

CMAR

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Background Circular RNAs (circRNAs) play a crucial role in a variety of cancers, including colorectal cancer (CRC). This study aimed to explore the role of hsa_circ_0136666 ( circ-PRKDC ) in CRC and its potential mechanism. Methods The levels of circ-PRKDC , miR-198 and discoidin domain receptor 1 ( DDR1 ) were measured using quantitative real-time polymerase chain reaction or Western blot. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell apoptosis and cycle were evaluated via flow cytometry. Cell migration and invasion were examined using transwell assay. CyclinD1 protein level was determined via Western blot. The interaction among circ-PRKDC , miR-198 and DDR1 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was performed to analyze tumor growth in vivo. Results Circ-PRKDC and DDR1 levels were increased, and miR-198 level was decreased in CRC tissues and cells. Circ-PRKDC depletion inhibited proliferation, migration and invasion, and expedited apoptosis and cell cycle arrest in SW480 and HCT116 cells. Silence of circ-PRKDC impeded CRC progression by sponging miR-198 . Overexpression of miR-198 hindered CRC development via targeting DDR1 . Moreover, circ-PRKDC silencing suppressed tumor growth in vivo. Conclusion Knockdown of circ-PRKDC inhibited CRC progression via modulating miR-198 / DDR1 pathway.

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Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis

Cited by 28 publications

References 37 publications

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET

miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

<p>Circ-PRKDC Facilitates the Progression of Colorectal Cancer Through miR-198/DDR1 Regulatory Axis</p>

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