Circular RNA circNHSL1 promotes gastric cancer progression through the miR-1306-3p/SIX1/vimentin axis

Zhu, Zhongqi; Rong, Zeyin; Luo, Zai; Yu, Zhuang; Zhang, Jing; Qiu, Zhengjun; Huang, Chen

doi:10.1186/s12943-019-1054-7

Cited by 98 publications

(99 citation statements)

References 45 publications

(45 reference statements)

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“…These data suggested that circRNA_100269 could inhibit the proliferation, migration and invasion while inducing the cell cycle arrest and apoptosis of GC cells by suppressing PI3K/Akt signaling pathway. In consistence with our ndings, recent studies also reported circRNAs including circNHSL1 and circNF1 could be novel gene regulators in GC, which can affect tumor progression through various signaling pathways (22)(23)(24)(25)(26)(27). Taken all together, our results revealed the essential roles of circRNA_100269/PI3K/Akt signaling on the modulation of GC progression.…”

Section: Discussionsupporting

confidence: 90%

Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

wang

liu

2020

Preprint

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Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice. Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p<0.05), while the levels of PI3K were notably increased (p<0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p<0.05), where circRNA_100269 and PI3K was inversely correlated (p<0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p<0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p<0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p<0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p<0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.

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Section: Discussionsupporting

confidence: 90%

Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

wang

liu

2020

Preprint

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“…Conversely, these results also indicate that high WTAP expression may have an effect on tumour immunosuppression. DLX2, DLX5, SIX1, HOXB5, HOXC6, HOXC8, RBM48 and KRAS are genes involved in the regulation of mRNA expression and transcription. m6A is an important type of RNA modification.…”

Section: Discussionmentioning

confidence: 99%

High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

Qiao

et al. 2020

J Cellular Molecular Medi

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Background: N6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in gastric cancer (GC) tumourigenesis, providing novel insights into the molecular pathogenesis of GC.However, the involvement of Wilms' tumour 1-associated protein (WTAP), a key component of m6A methylation, in GC progression is controversial. Here, we investigated the biological role and underlying mechanism of WTAP in GC. Methods: We determined WTAP expression using tissue microarrays and The CancerGenome Atlas (TCGA) data set, which was used to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). CIBERSORT was used to determine WTAP expression in 22 immune cell types. Results:Wilms' tumour 1-associated protein was highly expressed in GC, which indicated a poor prognosis, and WTAP expression served as an independent predictor of GC survival. By WGCNA, GO, KEGG and core gene survival analyses, we found that high WTAP expression correlated with RNA methylation and that low expression correlated with a high T cell-related immune response. CIBERSORT was used to correlate low WTAP expression with T lymphocyte infiltration. Conclusion: RNA methylation and lymphocyte infiltration are the main causes of high WTAP expression and poor prognosis, respectively. K E Y W O R D S differentially expressed genes, DNA methylation, gastric cancer, N6-methyladenosine (m6A) methylation, WTAP | 4453 LI et aL.

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“…Transcription factors played a significant role in the development of tumors. Our recent study suggested that SIX1 could promote cancer cell migration and invasion through increasing vimentin expression at the transcriptional level directly by binding to the promoter domain of vimentin in gastric cancer 37 . Our previous studies found that KLF4 was downregulated both in gastric cancer and pancreatic cancer and regulated the expression of a vast number of oncogenes that are involved in many cellular functions, ranging from differentiation to growth, metastasis, and EMT.…”

Section: Discussionmentioning

confidence: 99%

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

et al. 2020

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| 1203 wileyonlinelibrary.com/journal/cas | INTRODUC TI ONColorectal cancer is the third most common tumor and the third leading cause of cancer-related death in man and women in the world. 1,2 In China, there was an increase of over 376 300 cases of CRC and a total of 191 000 deaths during 2015. 3 Environmental and lifestyle changes, including an altered diet, lack of appropriate physical activity, circadian disruption, and increase in alcohol consumption, have enormously aggravated the burden of CRC. 4 In the past several years, the incidence and mortality of CRC increased rapidly and the onset age was muchThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractGINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G 1 /S phase cell cycle in eukaryotes, however, its functional roles and molecular mechanisms remain unclear in many aspects. Our study was designed to investigate the clinical significance, biological function, and molecular mechanism of GINS4 in colorectal cancer (CRC). First, we confirmed that GINS4 expression was significantly overexpressed in CRC cells and tissues. The immunohistochemical results in tissue microarray from 106 CRC patients showed that a high level of GINS4 expression was positively correlated with advanced T stage, higher tumor TNM stage, and poor differentiation. The results from univariate and multivariate survival analysis models based on 106 CRC patients revealed that GINS4 might serve as an independent prognostic indicator for overall survival and disease-free survival of CRC patients.Moreover, downregulated GINS4 can inhibit growth and the cell cycle and accelerate cell apoptosis progression in vitro as well as inhibit tumorigenesis in vivo. Besides, our results also indicated that Krüppel-like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of CRC. K E Y W O R D Sbiomarker, colorectal cancer, GINS4, growth, KLF4

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Circular RNA circNHSL1 promotes gastric cancer progression through the miR-1306-3p/SIX1/vimentin axis

Cited by 98 publications

References 45 publications

Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

High expression of WTAP leads to poor prognosis of gastric cancer by influencing tumour‐associated T lymphocyte infiltration

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

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