Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis

Guo, Xiaofeng; Zhou, Quanbo; Su, Dan; Luo, Yuming; Fu, Zhiqiang; Huang, Liqin; Li, Zhiguo; Jiang, Decan; Kong, Yao; Li, Zhihua; Chen, Rufu; Chen, Changhao

doi:10.1186/s12943-020-01196-4

Cited by 94 publications

(85 citation statements)

References 46 publications

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“…13,14 Accumulating studies have reported that circRNAs are widely detected in a variety of cancers and play an indispensable regulatory role in tumor development and progression. 15,16 Herein, we report a novel circRNA, circEHBP1 (hsa_circ_0005552), which was markedly upregulated in BCa and correlated positively with the prognosis of patients with BCa. circEHBP1 overexpression induced lymphangiogenesis and LN metastasis of BCa in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling

et al. 2021

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Lymphatic metastasis constitutes a leading cause of recurrence and mortality in bladder cancer. Accumulating evidence indicates that lymphangiogenesis is indispensable to trigger lymphatic metastasis. However, the specific mechanism is poorly understood. In the present study, we revealed a pathway involved in lymphatic metastasis of bladder cancer, in which a circular RNA (circRNA) facilitated lymphangiogenesis in a vascular endothelial growth factor C (VEGF-C)-independent manner. Novel circRNA circEHBP1 was markedly upregulated in bladder cancer and correlated positively with lymphatic metastasis and poor prognosis of patients with bladder cancer. circEHBP1 upregulated transforming growth factor beta receptor 1 (TGFBR1) expression through physically binding to miR-130a-3p and antagonizing the suppression effect of miR-130a-3p on the 3 0 UTR region of TGFBR1. Subsequently, cir-cEHBP1-mediated TGFbR1 overexpression activated the TGF-b/SMAD3 signaling pathway, thereby promoting the secretion of VEGF-D and driving lymphangiogenesis and lymphatic metastasis in bladder cancer. Importantly, administration of VEGF-D neutralizing antibodies remarkably blocked circEHBP1-induced lymphangiogenesis and lymphatic metastasis in vivo. Our findings highlighted that the circEHBP1/ miR-130a-3p/TGFbR1/VEGF-D axis contributes to lymphangiogenesis and lymphatic metastasis of bladder cancer independent of VEGF-C, which might lead to the development of cir-cEHBP1 as a potential biomarker and promising therapeutic target for lymphatic metastasis in bladder cancer.

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Section: Introductionmentioning

confidence: 99%

circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling

et al. 2021

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“…For instance, upregulated circ_0030235 facilitates PDAC cell growth and migratory and invasive potential, partly by inhibiting and sponging miR-1253 and miR-1294 [ 21 ]. Highly expressed circBFAR is also correlated with the poorer prognosis of patients with PDAC and promoted the progression of PDAC cells by sponging miR-34b-5p to activate the mesenchymal-epithelial transition factor (MET)/PI3K/Akt signaling pathway [ 22 ]. Hence, the evidence has been obtained to support the clinical significance of investigating the functional roles of circRNAs in PDAC and many circRNAs remain to be discovered.…”

Section: Introductionmentioning

confidence: 99%

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

Zhu

Zhou

Zhu

et al. 2021

Mediators of Inflammation

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Emerging evidence has shown that circular RNAs (circRNAs) and DNA methylation play important roles in the causation and progression of cancers. However, the roles of circRNAs and abnormal methylation genes in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. Expression profiles of circRNA, gene methylation, and mRNA were downloaded from the GEO database, and differentially expressed genes were obtained via GEO2R, and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Inflammation-associated genes were collected from the GeneCards database. Then, functional enrichment analysis and protein-protein interaction (PPI) networks of inflammation-associated methylated expressed genes were investigated using Metascape and STRING databases, respectively, and visualized in Cytoscape. Hub genes of PPI networks were identified using the NetworkAnalyzer plugin. Also, we analyzed the methylation, protein expression levels, and prognostic value of hub genes in PDAC patients through the UALCAN, Human Protein Atlas (HPA), and Kaplan-Meier plotter databases, respectively. The circRNA_102049/miR-455-3p/CD80 axis was identified by the ceRNA network and hub genes. In vitro and in vivo experiments were performed to evaluate the functions of circRNA_102049. The regulatory mechanisms of circRNA_102049 and miR-455-3p were explored by RT-PCR, western blot, and dual-luciferase assays. In the present study, twelve hub genes (STAT1, CCND1, KRAS, CD80, ICAM1, ESR1, RAF1, RPS6KA2, KDM6B, TNRC6A, FOSB, and DNM1) were determined from the PPI networks. Additionally, the circRNA_102049 was upregulated in PDAC cell lines. Functionally, the knockdown of circRNA_102049 by siRNAs inhibited cell growth, inflammatory factors, and migratory and invasive potential and promoted cell apoptosis. Mechanistically, circRNA_102049 functioned as a sponge of miR-455-3p and partially reversed the effect of miR-455-3p and consequently upregulated CD80 expression. Our findings showed that circRNA_102049 and methylated hub genes play an important role in the proliferation, apoptosis, migration, invasion, and inflammatory response of PDAC, which might be selected as a promising prognostic marker and therapeutic target for PDAC.

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“…Successfully accomplishing multi-omics data integration by systems biology approaches will fulfill future expectations and the need for robust, accurate, and feasible biomarker panels for pancreatic cancer. [166] Tumor tissue hsa_circ_0006215 Upregulated circRNA overexpression [167] Tumor tissue, plasma exosome circ-IARS Upregulated circRNA overexpression [168] Tumor tissue circ-PDE8A Upregulated circRNA overexpression [169] Tumor tissue/cell hsa_circ_0001649 Downregulated Microarray/qRT-PCR [170] Tumor tissue/cell hsa_circ_0005397 (circ-RHOT1) Upregulated Microarray/qRT-PCR [171] Tumor tissue/cell lines hsa_circ_0030235 Upregulated circRNA overexpression [172] Tumor tissue/cell lines hsa_circ_0007534 Upregulated circRNA overexpression [173] Tumor tissue/cell lines ciRS-7 (Cdr1as) Upregulated qRT-PCR [174] Tumor tissue hsa_circ_0007334 Upregulated Microarray/qRT-PCR [175] Tumor tissue circLDLRAD3 Upregulated circRNA knockdown [176] Tumor tissue/cell circASH2L Upregulated Microarray/qRT-PCR [177] Tumor tissue/cell lines circADAM9 Upregulated circRNA knockdown [178] Tumor tissue/cell hsa_circ_001653 Upregulated circRNA knockdown [179] Tumor tissue/cell circHIPK3 Upregulated circRNA knockdown [180] Tumor tissue/cell circFOXK2 Upregulated circRNA knockdown [181] Tumor tissue hsa_circ_0009065 (circBFAR) Upregulated circRNA overexpression [70] Tumor tissue hsa_circ_0086375 (circNFIB1) Downregulated circRNA knockdown [182] Tumor tissue/cell hsa_circ_0013912 Upregulated circRNA overexpression [183] Tumor tissue/cell lines hsa_circ_001587 Downregulated circRNA knockdown [184] Tumor [194] Tumor tissue BC008363 Upregulated Microarray/qRT-PCR [195] Tumor tissue HSATII Upregulated RNA-seq [196] Serum/plasma U2snRNA Upregulated Microarray/qRT-PCR [197] Pancreatic * CZE: capillary zone electrophoresis, ELISA: enzyme-linked immunosorbent assay, ELLA: Enzyme-linked lectin assay, FISH: fluorescence in situ hybridization, GC: gas chromatography, HILIC: Hydrophilic interaction chromatography, HRMAS: high-resolution magic angle spinning, LC: liquid chromatography, MS: mass spectrometry, NMR: nuclear magnetic resonance, qRT-PCR: quantitative reverse transcription polymerase chain reaction, TOF: time of flight, WB: Western blot, WES: Whole exome sequencing, WGS: whole genome ...…”

Section: Resultsmentioning

confidence: 99%

Current State of “Omics” Biomarkers in Pancreatic Cancer

Turanlı

Yildirim

Gulfidan

et al. 2021

JPM

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Pancreatic cancer is one of the most fatal malignancies and the seventh leading cause of cancer-related deaths related to late diagnosis, poor survival rates, and high incidence of metastasis. Unfortunately, pancreatic cancer is predicted to become the third leading cause of cancer deaths in the future. Therefore, diagnosis at the early stages of pancreatic cancer for initial diagnosis or postoperative recurrence is a great challenge, as well as predicting prognosis precisely in the context of biomarker discovery. From the personalized medicine perspective, the lack of molecular biomarkers for patient selection confines tailored therapy options, including selecting drugs and their doses or even diet. Currently, there is no standardized pancreatic cancer screening strategy using molecular biomarkers, but CA19-9 is the most well known marker for the detection of pancreatic cancer. In contrast, recent innovations in high-throughput techniques have enabled the discovery of specific biomarkers of cancers using genomics, transcriptomics, proteomics, metabolomics, glycomics, and metagenomics. Panels combining CA19-9 with other novel biomarkers from different “omics” levels might represent an ideal strategy for the early detection of pancreatic cancer. The systems biology approach may shed a light on biomarker identification of pancreatic cancer by integrating multi-omics approaches. In this review, we provide background information on the current state of pancreatic cancer biomarkers from multi-omics stages. Furthermore, we conclude this review on how multi-omics data may reveal new biomarkers to be used for personalized medicine in the future.

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Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis

Cited by 94 publications

References 46 publications

circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling

circEHBP1 promotes lymphangiogenesis and lymphatic metastasis of bladder cancer via miR-130a-3p/TGFβR1/VEGF-D signaling

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p

Current State of “Omics” Biomarkers in Pancreatic Cancer

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