Upregulated miR‐1258 regulates cell cycle and inhibits cell proliferation by directly targeting E2F8 in <scp>CRC</scp>

Zhang, Zhiyuan; Li, Jie; Huang, Yuesheng; Peng, Wen; Qian, Wenwei; Gu, Jiou; Wang, Hongtao; Hu, Tao; Ji, Dongjian; Ji, Bing; Zhang, Yue; Wang, Shijia; Sun, Yueming

doi:10.1111/cpr.12505

Cited by 84 publications

(84 citation statements)

References 26 publications

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“…E2F8 has been reported to overexpress in lung cancer, breast cancer, colorectal cancer, ovarian cancer, prostate cancer, esophageal squamous cell carcinoma and HCC [8,[29][30][31][32][33]. Consistently, our results also indicated that E2F8 was up-regulated in HCC tumors and correlated with advanced tumor stage and AFP elevation.…”

Section: Discussionsupporting

confidence: 87%

Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report

Lü

Zhang

et al. 2020

Bioscience Reports

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This report aimed to investigate the carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma (HCC). E2F8 expression level was compared in Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and Oncomine. Survival analysis of E2F8 for HCC were conducted in Kaplan–Meier plotter. Correlations of E2F8 and clinico-pathological features were performed in TCGA. Enrichment of interacted and similar genes with E2F8 was evaluated in Gene Set Enrichment Analysis (GSEA) and Metascape. We found that E2F8 was significantly up-regulated in tumor tissues compared with nontumor tissues (all P < 0.01). Moreover, E2F8 was significantly overexpressed in peripheral blood mononuclear cell (PBMC) in HCC patients than that in healthy individuals (P < 0.001). Meta-analysis in Oncomine database confirmed that E2F8 was significantly higher in HCC tumors (P = 4.28E-08). Additionally, E2F8 elevation significantly correlated with overall survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS) and progression-free survival (PFS) in HCC patients (all P < 0.01). E2F8 level was significantly higher in HCC patients with advanced neoplasm histologic grade, American Joint Committee on Cancer (AJCC) stage and α-fetoprotein (AFP) elevation (all P < 0.05). Cox regression model demonstrated that high E2F8 was an independent risk factor for OS and DFS in HCC patients (HR = 2.16, P = 0.003 and HR = 1.64, P = 0.002, respectively). Enrichment analysis revealed that genes interacted/similar with E2F8 were mainly enriched in cell cycle pathways/biological process. Conclusively, up-regulated in tumors, E2F8 might accelerate tumor progression and result in unfavorable outcomes in HCC patients.

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Section: Discussionsupporting

confidence: 87%

Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report

Lü

Zhang

et al. 2020

Bioscience Reports

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“…Procedures were described previously (24). LV2-hsa-miR-1224-5p-mimic vector (miR-1224-5p-mimics), LV2-hsa-miR-1224-5p-inhibitor vector (miR-1224-5p-inhibitor), and LV2 empty lentivirus as a negative control (miR-NC) were constructed by lentiviral vectors (GenePharma, Shanghai, China).…”

Section: Cell Transfectionmentioning

confidence: 99%

“…Report assay was conducted as previously described (24). The wild-type 3 ′ -UTR sequence of SP1 predicted to interact with miR-1224-5p, referred to as WT-SP1 3 ′ -UTR, together with a matched mutated sequence within potential binding sites, referred to as MUT-SP1 3 ′ -UTR, were synthesized by GenScript (Nanjing, China).…”

Section: Luciferase Report Assaymentioning

confidence: 99%

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MicroRNA-1224-5p Inhibits Metastasis and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting SP1-Mediated NF-κB Signaling Pathways

Peng

Yang

et al. 2020

Front. Oncol.

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MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in cancer initiation and progression. However, the roles and molecular mechanisms of miRNAs in colorectal cancer (CRC) progression remain unclear. Here, we show that downregulation of miR-1224-5p in CRC is negatively correlated with SP1 expression and metastasis in patients and xenografted mouse models. Gain-and loss-of-function assays reveal that miR-1224-5p suppresses the migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells in vitro and in vivo by directly targeting SP1. Moreover, SP1 promotes the phosphorylation of p65, which results in EMT progress in CRC cells. Clinical analysis reveals that miR-1224-5p and SP1 expression are remarkably associated with advanced clinical features and unfavorable prognosis of patients with CRC. Further study confirms that hypoxia accounts for the depletion of miR-1224-5p in CRC. The enhancement of hypoxia during epithelial-mesenchymal transition and metastasis of CRC cells is abolished by miR-1224-5p. Our findings provide the first evidence that miR-1224-5p is a potential therapeutic target and prognostic biomarker for patients with CRC.

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“…Some miRNAs were reported to be associated with above biological processes in cancers. miR-661 and miR-22 were reported to regulate chromatin remodeling [35,36], miR-122, miR-15a, miR-26, miR-29, mir-30 and let-7 were related to the transcriptional misregulation in cancer [37], miR-188, miR-638 and miR-1258 were involved in the cell cycle regulation [38][39][40].…”

Section: Function Of the Four Mirnasmentioning

confidence: 99%

A Novel Four-MicroRNA Signature for Prognosis and Diagnosis in Colorectal Cancer

Chen

Qin

Zhou

et al. 2020

Preprint

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Background and aims: Colorectal cancer (CRC) remains a global public health problem. We aimed to access prognostic microRNAs (miRNAs) associated with overall survival (OS) and evaluate their diagnostic value in CRC.Methods: Three serum miRNA expression profiles from Gene Expression Omnibus (GEO) database and tissue miRNA expression profile of CRC from The Cancer Genome Atlas (TCGA) database were studied to get common differentially expressed miRNA (DEmiRNAs) in serums and tissues. 569 CRC patients with survival information from TCGA database were randomly divided into the discovery and validation cohort. Based on the TCGA discovery cohort, the univariate cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate cox proportional hazards regression analysis were performed and a prognostic signature was constructed. The prognostic capacity of the signature was verified in TCGA validation cohort and the prognostic signature expression in tumors and serums was validated in an independent microarray dataset and our clinical set. We also evaluated the diagnostic power of the model in serum by calculating the area under the receiver operating characteristic (ROC) curve in a clinical set. Functional enrichment analyses were applied to analyze the potential roles of the signature in CRC.Results: A total of 154 common DEmiRNAs were identified. Based on the TCGA discovery cohort, a four-miRNA (miR-10b, miR-130a, miR-561, miR-4684) prognostic signature was constructed and a predictive nomogram model including the expression of above four miRNAs showed good performance for predicting the 3- and 5-year overall survival. The findings were well verified in TCGA validation cohort. miR-10b, miR-130a, miR-561 and miR-4684 were significantly upregulated both in CRC tumors and serums. Circulating miR-10b, miR-130a, miR-561 and miR-4684 levels were significantly downregulated after surgical resection of tumor in CRC patients, suggesting these four circulating miRNAs in the serum were tumor derived. The four circulating miRNA combination might act as a novel diagnostic signature for CRC. Functional enrichment analyses suggested that above four miRNAs might be related to the progression of CRC. Conclusions: We developed a novel reliable prognostic and diagnostic signature, which should be beneficial for CRC screening and clinical therapeutic decision-making.

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Upregulated miR‐1258 regulates cell cycle and inhibits cell proliferation by directly targeting E2F8 in CRC

Abstract: MiR-1258 may function as a suppressive factor by negatively controlling E2F8, thus, highlighting the potential role of miR-1258 as a therapeutic target for human CRC.

Cited by 84 publications

References 26 publications

Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report

Carcinogenesis effects of E2F transcription factor 8 (E2F8) in hepatocellular carcinoma outcomes: an integrated bioinformatic report

MicroRNA-1224-5p Inhibits Metastasis and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting SP1-Mediated NF-κB Signaling Pathways

A Novel Four-MicroRNA Signature for Prognosis and Diagnosis in Colorectal Cancer

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