Up‐regulation of ZFAS1 indicates dismal prognosis for cholangiocarcinoma and promotes proliferation and metastasis by modulating USF1 via miR‐296‐5p

Li, Zhenglong; Jiang, Xingming; Huang, Liyi; Li, Jinglin; Ji, Daolin; Xu, Yi; Leng, Kaiming; Cui, Yunfu

doi:10.1111/jcmm.14698

Cited by 19 publications

(12 citation statements)

References 33 publications

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“…Based on the above results, we found that the up-regulation of HAS2-AS1 was related to the development of glioma, thus, it is necessary to explore the underlying molecular mechanism. Several studies have demonstrated that lncRNAs can be activated by their upstream transcription factors [15,19,20]. The transcription factors that regulate the expression of HAS2-AS1 were predicted through the hTFtarget database, and USF1 was selected as the object.…”

Section: Usf1 Activates the Expression Of Has2-as1 By Binding To The mentioning

confidence: 99%

The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1

Wang

You

et al. 2020

Bioscience Reports

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Objective: The role of lncRNAs in tumor has been widely concerned. This study took HAS2-AS1 as a starting point to explore its expression in glioma and its role in the process of migration and invasion, providing a strong theoretical basis for mining potential therapeutic targets of glioma. Methods: Clinical data of glioma were obtained from TCGA database and differentially expressed lncRNAs were analyzed by edgeR. The hTFtarget database was used to predict the upstream transcription factors of HAS2-AS1 and the JASPAR website was used to predict the binding sites of human upstream transcription factor 1 (USF1) and HAS2-AS1. qRT-PCR was used to detect the expressions of HAS2-AS1 and USF1 in glioma tissues and cell lines. The effects of silencing HAS2-AS1 on the migration and invasion of cancer cells were verified by wound healing and Transwell invasion assays. The ChIP and dual luciferase reporter assays were applied to demonstrate the binding of USF1 and HAS2-AS1 promoter region. Western blot was used to detect the expressions of EMT-related proteins. Results: HAS2-AS1 was highly expressed in glioma tissues and cells, and was significantly associated with poor prognosis. Silencing HAS2-AS1 expression inhibited glioma cell migration, invasion and EMT. USF1 was highly expressed in glioma and positively correlated with HAS2-AS1. The transcription of HAS2-AS1 was activated by USF1 via binding to HAS2-AS1 promoter region, consequently potentiating the invasion and migration abilities of glioma cells. Conclusion: These results suggested that the transcription factor USF1 induced upregulation of lncRNA HAS2-AS1 and promoted glioma cell invasion and migration.

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Section: Usf1 Activates the Expression Of Has2-as1 By Binding To The mentioning

confidence: 99%

The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1

Wang

You

et al. 2020

Bioscience Reports

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“…The included 2263 patients all come from China. 16 types of tumors were included in this study, which contains pancreatic adenocarcinoma (PAAD) [10], hepatocellular carcinoma (HCC) [11,18], melanoma [12], esophageal squamous cell carcinoma (ESCC) [13,19], hepatoblastoma (HB) [20], cholangiocarcinoma (CCA) [14], papillary thyroid carcinoma (PTC) [21], prostate cancer (PCa) [22], clear cell renal cell carcinoma (ccRCC) [15], colorectal cancer (CRC) [16,23,24], bladder cancer [25,26], nasopharyngeal carcinoma (NPC) [27], gastric cancer (GC) [28], epithelial ovarian cancer (EOC) [29], non-small cell lung cancer (NSCLC) [30], glioma [31]. ZFAS1 expression in tumor tissues were all detected by qRT-PCR.…”

Section: Details Of Included Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Growing studies have reported abnormal expression of ZFAS1 in diverse cancers, including pancreatic cancer [10], hepatocellular carcinoma [11], melanoma [12], esophageal squamous cell carcinoma [13] and so on. Moreover, elevated ZFAS1 expression is reported to be related to poor prognosis and clinical characteristics in various cancers [14][15][16], which indicate that ZFAS1 may serve as a promising biomarker for the prognosis and therapy of cancer patients.However, limited by insu cient sample size in single study and inconsistent ndings among studies, the clinical role of ZFAS1 in cancer deserve further study to con rm. So we performed this updated meta-analysis to comprehensively evaluate the association between ZFAS1 expression and OS and clinicopathological characteristics of cancer patients.…”

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confidence: 99%

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Clinical value of lncRNA ZFAS1 in various cancers: an updated meta-analysis of 2263 cancer patients

Liu

Chen

et al. 2020

Preprint

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Background: LncRNA ZNFX1 antisense RNA 1 (ZFAS1) is largely reported to be abnormally expressed in various human cancers and associated with unfavorable prognosis. So this study aims to further investigate its clinical value in multifarious cancers.Methods: Databases of PubMed, Web of science, Cochrane library, Embase, Chinese National Knowledge Infrastructure and Wanfang was retrieved to collect eligible studies until October 22, 2020. The clinical role of ZFAS1 was comprehensively assessed by STATA 12.0. Additionally, the CeRNA network in which ZFAS1 involved was constructed. And function analysis of targeted mRNAs was performed by R package “cluster profiler”.Results: 23 studies of 2263 cancer patients met the inclusion criteria in this meta-analysis. The comprehensive results suggested that patients with elevated ZFAS1 expression got poor overall survival (OS) (HR=1.80, 95%CI: 1.50-2.10, P≤0.001), and they are prone to lymph node metastasis (OR=2.67, 95%CI: 1.73-4.14, P≤0.001), distant metastasis (DM) (OR=3.45, 95%CI: 1.61-7.39, P=0.001), advanced TNM stage (HTS) (OR=2.99, 95%CI: 1.97-4.54, P≤0.001), larger tumor size (LTS) (OR=1.54, 95%CI: 1.05-2.24, P≤0.001), poor histologic grade (PHG) (OR=1.57, 95%CI: 1.09-2.26, P=0.015). The CeRNA network and function analysis revealed the potential mechanism which ZFAS1 may involve in cancers.Conclusion: The current analysis revealed that elevated ZFAS1 expression is common in various cancer and was significantly associated with poor OS and clinical characteristics, thus it may function as prognostic biomarker in various cancer. Nevertheless, larger well-designed clinical research a is still warranted to verify our findings.

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“…Recently, researchers have become very interested in their role in tumour invasion, metastasis, and signalling pathways, and previous studies have demonstrated the involvement of lncRNAs as key molecules in the malignant biology of various cancers [ 8 – 10 ]. At present, some studies have described the relevant roles of fractional lncRNAs in cholangiocarcinoma [ 11 – 13 ], but the role of more lncRNAs in the malignant progression of intrahepatic cholangiocarcinoma still needs to be further identified and analysed.…”

Section: Introductionmentioning

confidence: 99%

A metabolism-related 4-lncRNA prognostic signature and corresponding mechanisms in intrahepatic cholangiocarcinoma

Zou

Wang

et al. 2021

BMC Cancer

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Background Long non-coding RNA (lncRNA) plays a critical role in the malignant progression of intrahepatic cholangiocarcinoma (iCCA). This study aimed to establish a 4-lncRNA prognostic signature and explore corresponding potential mechanisms in patients with iCCA. Methods The original lncRNA-seq and clinical data were collected from the TCGA and GEO databases. Overlapping and differentially expressed lncRNAs (DE-lncRNAs) were further identified from transcriptome data. Univariate regression analysis was performed to screen survival-related DE-lncRNAs, which were further selected to develop an optimal signature to predict prognosis using multivariate regression analysis. The Kaplan-Meier survival curve visualized the discrimination of the signature on overall survival (OS). The area under the curve (AUC) and C-index were used to verify the predictive accuracy of the signature. Combined with clinical data, multivariate survival analysis was used to reveal the independent predictive capability of the signature. In addition, a prognostic nomogram was constructed. Finally, the common target genes of 4 lncRNAs were predicted by the co-expression method, and the corresponding functions were annotated by GO and KEGG enrichment analysis. Gene set enrichment analysis (GSEA) was also performed to explore the potential mechanism of the signature. Quantitative real-time PCR was used to evaluated the expression of 4 lncRNAs in an independent cohort. Results We identified and constructed a 4-lncRNA (AC138430.1, AGAP2-AS1, AP001783.1, and AP005233.2) prognostic signature using regression analysis, and it had the capability to independently predict prognosis. The AUCs were 0.952, 0.909, and 0.882 at 1, 2, and 3 years, respectively, and the C-index was 0.808, which showed good predictive capability. Subsequently, combined with clinical data, we constructed a nomogram with good clinical application. Finally, 252 target genes of all four lncRNAs were identified by the co-expression method, and functional enrichment analysis showed that the signature was strongly correlated with metabolism-related mechanisms in tumourigenesis. The same results were also validated via GSEA. Conclusion We demonstrated that a metabolism-related 4-lncRNA prognostic signature could be a novel biomarker and deeply explored the target genes and potential mechanism. This study will provide a promising therapeutic strategy for patients with intrahepatic cholangiocarcinoma.

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Up‐regulation of ZFAS1 indicates dismal prognosis for cholangiocarcinoma and promotes proliferation and metastasis by modulating USF1 via miR‐296‐5p

Cited by 19 publications

References 33 publications

The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1

The transcription factor USF1 promotes glioma cell invasion and migration by activating lncRNA HAS2-AS1

Clinical value of lncRNA ZFAS1 in various cancers: an updated meta-analysis of 2263 cancer patients

A metabolism-related 4-lncRNA prognostic signature and corresponding mechanisms in intrahepatic cholangiocarcinoma

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