Circular RNA Expression Profile of Pancreatic Ductal Adenocarcinoma Revealed by Microarray

Background/Aims: Circular RNAs (circRNAs) are a special novel type of a stable, diverse and conserved noncoding RNA in mammalian cells. Particularly in cancer, circRNAs have been reported to be widely involved in the physiological/pathological process of life. However, it is unclear whether circRNAs are specifically involved in pancreatic ductal adenocarcinoma (PDAC). Methods: We investigated the expression profile of circRNAs in six PDAC cancer samples and paired adjacent normal tissues using microarray. A high-throughput circRNA microarray was used to identify dysregulated circular RNAs in six PDAC patients. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. Results: We revealed and confirmed that a number of circRNAs were dysregulated, which suggests a potential role in pancreatic cancer. Conclusions: this study demonstrates that clusters of circRNAs are aberrantly expressed in PDAC compared with normal samples and provides new potential targets for the future treatment of PDAC and novel insights into PDAC biology.

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Microarray expression profile of circular RNAs in human pancreatic ductal adenocarcinoma

Genomics Data ◽

10.1016/j.gdata.2015.07.017 ◽

2015 ◽

Vol 5 ◽

pp. 385-387 ◽

Cited By ~ 53

Author(s):

Shibin Qu ◽

Wenjie Song ◽

Xisheng Yang ◽

Jianlin Wang ◽

Ruohan Zhang ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Expression Profile ◽

Ductal Adenocarcinoma ◽

Circular Rnas ◽

Microarray Expression ◽

Microarray Expression Profile

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CircMYOF triggers progression and facilitates glycolysis via the VEGFA/PI3K/AKT axis by absorbing miR-4739 in pancreatic ductal adenocarcinoma

Cell Death Discovery ◽

10.1038/s41420-021-00759-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Dandan Zheng ◽

Xianxian Huang ◽

Juanfei Peng ◽

Yanyan Zhuang ◽

Yuanhua Li ◽

...

Keyword(s):

Glucose Metabolism ◽

Pancreatic Ductal Adenocarcinoma ◽

Circular Rna ◽

Ductal Adenocarcinoma ◽

Luciferase Reporter ◽

Circular Rnas ◽

Loss Of Function ◽

Competing Endogenous Rna ◽

Rnase R

AbstractEmerging evidence has demonstrated that circular RNAs (circRNAs) take part in the initiation and development of pancreatic ductal adenocarcinoma (PDA), a deadly neoplasm with an extremely low 5-year survival rate. Reprogrammed glucose metabolism is a key feature of tumour development, including PDA. In this research, we evaluated the role of circRNAs in reprogrammed glucose metabolism in PDA. RNA sequencing under various glucose incubation circumstances was performed. A new circMYOF was identified. Sanger sequencing and RNase R treatment confirmed its circular RNA characteristics. Real-time PCR indicated that it was highly expressed in PDA clinical specimens and cell lines. Gain-of- and loss-of-function assays showed that circMYOF induced progression in PDA. Mechanistically, RNA pull-down and luciferase reporter experiments elucidated that circMYOF, as a competing endogenous RNA for miR-4739, facilitated glycolysis via the VEGFA/PI3K/AKT pathway. Taken together, our findings indicate that circMYOF may work as a desirable biomarker and therapeutic target for PDA patients.

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Downregulated Expression of hsa_circ_0005556 in Gastric Cancer and Its Clinical Significance

Disease Markers ◽

10.1155/2019/2624586 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Liangwei Yang ◽

Yu Yu ◽

Xiuchong Yu ◽

Jiaming Zhou ◽

Zhiping Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Roc Curve ◽

Noncoding Rna ◽

Operating Characteristic ◽

Diagnostic Value ◽

Circular Rnas ◽

Normal Tissues ◽

Potential Biomarker ◽

Polymerase Chain

Background. Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. Materials and Methods. The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. Results. hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n=100, p<0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p=0.001), TNM stage (p=0.013), and lymphatic metastasis (p=0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p=0.047). Conclusion. hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).

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The circular RNA expression profile in ovarian serous cystadenocarcinoma reveals a complex circRNA–miRNA regulatory network

BMC Medical Genomics ◽

10.1186/s12920-021-01132-5 ◽

2021 ◽

Vol 14 (S2) ◽

Author(s):

Minhui Zhuang ◽

Jian Zhao ◽

Jing Wu ◽

Shilong Fu ◽

Ping Han ◽

...

Keyword(s):

Potential Function ◽

Expression Profile ◽

Regulatory Network ◽

Noncoding Rna ◽

Interaction Network ◽

Enrichment Analysis ◽

Circular Rna ◽

Mirna Sponge ◽

Normal Tissues ◽

Serous Cystadenocarcinoma

Abstract Background Ovarian serous cystadenocarcinoma is one of the most serious gynecological malignancies. Circular RNA (circRNA) is a type of noncoding RNA with a covalently closed continuous loop structure. Abnormal circRNA expression might be associated with tumorigenesis because of its complex biological mechanisms by, for example, functioning as a microRNA (miRNA) sponge. However, the circRNA expression profile in ovarian serous cystadenocarcinoma and their associations with other RNAs have not yet been characterized. The main purpose of this study was to reveal the circRNA expression profile in ovarian serous cystadenocarcinoma. Methods We collected six specimens from three patients with ovarian serous cystadenocarcinoma and adjacent normal tissues. After RNA sequencing, we analyzed the expression of circRNAs with relevant mRNAs and miRNAs to characterize potential function. Results 15,092 unique circRNAs were identified in six specimens. Approximately 46% of these circRNAs were not recorded in public databases. We then reported 353 differentially expressed circRNAs with oncogenes and tumor-suppressor genes. Furthermore, a conjoint analysis with relevant mRNAs revealed consistent changes between circRNAs and their homologous mRNAs. Overall, construction of a circRNA–miRNA network suggested that 4 special circRNAs could be used as potential biomarkers. Conclusions Our study revealed the circRNA expression profile in the tissues of patients with ovarian serous cystadenocarcinoma. The differential expression of circRNAs was thought to be associated with ovarian serous cystadenocarcinoma in the enrichment analysis, and co-expression analysis with relevant mRNAs and miRNAs illustrated the latent regulatory network. We also constructed a complex circRNA–miRNA interaction network and then demonstrated the potential function of certain circRNAs to aid future diagnosis and treatment.

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Novel circular RNA circSLIT2 facilitates the aerobic glycolysis of pancreatic ductal adenocarcinoma via miR-510-5p/c-Myc/LDHA axis

Cell Death and Disease ◽

10.1038/s41419-021-03918-y ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Hua Guan ◽

Wei Luo ◽

Yuping Liu ◽

Mingfei Li

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Aerobic Glycolysis ◽

Circular Rna ◽

Ductal Adenocarcinoma ◽

Circular Rnas ◽

The Novel ◽

Mirna Sponge ◽

Promising Therapeutic Target

AbstractIncreasing evidence has indicated the great diagnostic and therapeutic potentials of circular RNAs (circRNAs) in human cancers. Although the biological roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) have been partially annotated, the potential regulatory mechanism of circRNAs in PDAC tumorigenesis remains poorly understood. Here, our study found that the novel circRNA circSLIT2 was significantly upregulated in PDAC tissues and cells. Clinically, ectopic high-expression of circSLIT2 was correlated with unfavorable prognosis of PDAC patients. Functional experiments demonstrated that circSLIT2 promoted the aerobic glycolysis and proliferation of PDAC cells in vitro, and circSLIT2 knockdown inhibited tumor growth in vivo. Mechanistically, circSLIT2 acted as miRNA sponge to target miR-510-5p/c-Myc axis. Furthermore, c-Myc bound with the promoter region of lactate dehydrogenase A (LDHA) to activate the transcription. Collectively, present findings reveal that circSLIT2/miR-510-5p/c-Myc/LDHA axis participates in the aerobic glycolysis and carcinogenesis of PDAC, and may act as a promising therapeutic target.

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Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis

Molecular Cancer ◽

10.1186/s12943-021-01400-z ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Zeyin Rong ◽

Si Shi ◽

Zhen Tan ◽

Jin Xu ◽

Qingcai Meng ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Energy Production ◽

Atp Synthesis ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Ductal Adenocarcinoma ◽

Luciferase Reporter ◽

Circular Rnas

Abstract Background Extensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. However, the expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. Methods CircEYA3 was explored based on Gene Expression Omnibus (GEO) dataset analysis. qRT-PCR was applied to determine the expression of circRNAs, miRNAs and mRNAs in PDAC cells and tissues. The biological roles of circEYA3 in vitro and in vivo were determined by performing a series of functional experiments. Further, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA pull-down assays, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of circEYA3 with miR-1294. Results CircEYA3 was elevated in PDAC tissues and cells, and a higher level of circEYA3 was significantly associated with a poorer prognosis in patients with PDAC. Functionally, circEYA3 increased energy production via ATP synthesis to promote PDAC progression in vitro and in vivo. Mechanistically, circEYA3 functions as an endogenous miR-1294 sponge to elevate c-Myc expression, thus exerting its oncogenic functions. Conclusion CircEYA3 promotes the progression of PDAC through the miR-1294/c-Myc signalling axis, and circEYA3 may be an efficient molecular therapeutic target in PDAC.

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Genome-wide identification and characterization of circular RNA m6A modification in pancreatic cancer

Genome Medicine ◽

10.1186/s13073-021-01002-w ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Ying Ye ◽

Weiyi Feng ◽

Jialiang Zhang ◽

Kaiyu Zhu ◽

Xudong Huang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Circular Rna ◽

Ductal Adenocarcinoma ◽

Circular Rnas ◽

Tissue Samples ◽

Normal Tissues ◽

Genome Wide ◽

Genomic Landscape ◽

Tumor Tissues

Abstract Background N6-methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m6A modifications in linear RNA, transcriptome-wide profiling and exploration of m6A modification in circular RNAs in cancer is still lacking. Methods For the detection of m6A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m6A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC). Results Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m6A modifications. By using Circm6A, we identified a total of 8807 m6A-circRNAs from our m6A-seq data. The m6A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m6A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m6A-circRNAs may promote the circularization and translation of circRNAs. Conclusions These comprehensive findings further bridged the knowledge gaps between m6A modification and circRNAs fields by depicting the m6A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m6A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a.

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Circular RNA expression profile in transgenic diabetic mouse kidneys

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00270-z ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Xuan Xiong ◽

Changchun Liu ◽

Meiren Shen ◽

Qian Yang ◽

Qiang Zhao ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Expression Profile ◽

Circular Rna ◽

Diabetic Mouse ◽

Differentially Expressed ◽

Circular Rnas ◽

Diabetic Mice ◽

Wild Type ◽

Patients With Diabetes ◽

Polymerase Chain

Abstract Background Diabetic nephropathy is one of the most important complications in patients with diabetes. The etiology and pathogenesis of diabetic nephropathy remain unclear. Several studies have indicated that circular RNAs (circRNAs) play crucial regulatory roles in numerous human diseases and normal physiology; however, to date, no study has focused on the comprehensive expression profile of circRNAs in the kidneys of diabetic mice. Therefore, we aimed to identify differentially expressed circRNAs in diabetic mouse kidneys to explore the possible roles of dysregulated circRNAs in diabetic nephropathy development. Results Diabetic BKS-Leprem2Cd479/Nju (BKS-DB/Nju) mice and their nondiabetic wild-type littermates of C57BL/KsJ wild-type (WT) mice were used as experimental animals. Among all circRNAs identified by high-throughput RNA sequencing, four circRNAs were upregulated and ten were downregulated in diabetic mouse kidneys compared to those in nondiabetic mouse kidneys. After verification using quantitative reverse transcriptase polymerase chain reaction assays, we found that circR_1084, circR_182, circR_4, circR_50, circR_596, circR_897, and circR_203 were downregulated, whereas circR_627, circR_628, circR_735, and circR_801 were upregulated in the renal tissues of 8- and 16-week-old BKS-DB/Nju mice compared to those in WT mice. Conclusion We studied the circRNA expression profile in the kidneys of diabetic mice. Differentially expressed circRNAs may be useful as candidate biomarkers for diabetic nephropathy. Collectively, our results provide a novel theoretical basis for further investigation of the regulatory roles of circRNA in the etiology and pathogenesis of diabetic nephropathy.

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Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽

10.1038/s41388-021-01762-0 ◽

2021 ◽

Vol 40 (17) ◽

pp. 3164-3179

Author(s):

Yang Liu ◽

Tianchi Tang ◽

Xiaosheng Yang ◽

Peng Qin ◽

Pusen Wang ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Noncoding Rna ◽

Pancreatic Tumor ◽

Epithelial Mesenchymal Transition ◽

Noncoding Rnas ◽

Ductal Adenocarcinoma ◽

Overall Survival Rate ◽

Poor Overall Survival ◽

Mesenchymal Transition ◽

Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

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The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01849-2 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Mingyi Zhou ◽

Zhuo Yang ◽

Danbo Wang ◽

Peng Chen ◽

Yong Zhang

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Cell Cycle Progression ◽

Critical Role ◽

Circular Rna ◽

Circular Rnas ◽

Cyclin E1 ◽

Normal Tissues ◽

Exact Function ◽

Potential Biomarker

Abstract Background As a novel type of non-coding RNA, circular RNAs (circRNAs) play a critical role in the initiation and development of various diseases, including cancer. However, the exact function of circRNAs in human cervical cancer remains largely unknown. Methods We identified the circRNA signature of upregulated circRNAs between cervical cancer and paired adjacent normal tissues. Using two different cohorts and GEO database, a total of six upregulated circRNAs were identified with a fold change > 2, and P < 0.05. Among these six circRNAs, hsa_circ_0072088 (circZFR) was the only exonic circRNA significantly overexpressed in cervical cancer. Functional experiments were performed to investigate the biological function of circZFR. CircRNA pull-down, circRNA immunoprecipitation (circRIP) and Co-immunoprecipitation (Co-IP) assays were executed to investigate the molecular mechanism underlying the function of circZFR. Results Functionally, circZFR knockdown represses the proliferation, invasion, and tumor growth. Furthermore, circRNA pull-down experiments combined with mass spectrometry unveil the interactions of circZFR with Single-Stranded DNA Binding Protein 1 (SSBP1). Mechanistically, circZFR bound with SSBP1, thereby promoting the assembly of CDK2/cyclin E1 complexes. The activation of CDK2/cyclin E1 complexes induced p-Rb phosphorylation, thus releasing activated E2F1 leading to cell cycle progression and cell proliferation. Conclusion Our findings provide the first evidence that circZFR is a novel onco-circRNA and might be a potential biomarker and therapeutic target for cervical cancer patients.

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