• diagnosis and prognosis
• epigenetic factors
• hepatocellular carcinoma
• miRNA sponge
• therapy resistance

• Humans
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/diagnosis
• Liver Neoplasms/genetics
• Liver Neoplasms/therapy
• Liver Neoplasms/diagnosis
• Gene Expression Regulation, Neoplastic
• Prognosis
• Biomarkers, Tumor/genetics
• RNA, Untranslated/genetics
• RNA, Long Noncoding/genetics
• Animals
• MicroRNAs/genetics

• Anti-tumor immunity
• Circular RNA
• Exosomes
• Hepatocellular carcinoma
• Mesenchymal stem cells
• Non-coding RNAs
• Tumor microenvironment

• Humans
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/therapy
• Liver Neoplasms/metabolism
• Exosomes/genetics
• Exosomes/metabolism
• Gene Expression Regulation, Neoplastic

• CRC
• cancer
• circRNA.
• lncRNA
• miRNA
• ncRNA

• Humans
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/therapy
• Biomarkers, Tumor/genetics
• RNA, Untranslated/genetics
• Gene Expression Regulation, Neoplastic
• Prognosis
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Predictive Value of Tests

• (EMR/2017/002874) Science and Engineering Research Board (SERB)
• BT/PR26189/GET/119/ 226 /2017 Dept. of Biotechnology, Govt. of India

• ADGRG2
• hepatocellular carcinoma
• immune inflammation
• miR-326
• neutrophil
• prognostic marker

• Humans
• Carcinoma, Hepatocellular/metabolism
• Cell Proliferation/genetics
• Liver Neoplasms/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Neutrophils/metabolism
• Prognosis
• Receptors, G-Protein-Coupled/genetics

• 31601036 National Natural Science Foundation of China
• 2021CFB190 Natural Science Foundation of Hubei Province
• Q20201314, B2017038 Scientific research plan project of Hubei Provincial Department of Education
• Yz2022232 Innovation and Entrepreneurship Training Program for College Students of Yangtze University

• Biomarker
• Circular RNA
• Liver cancer
• Prognosis

• Humans
• Carcinoma, Hepatocellular/pathology
• RNA, Circular/genetics
• Up-Regulation
• Liver Neoplasms/pathology
• MicroRNAs/metabolism
• Biomarkers/analysis

• 2021BC002 Science and Technology Cooperation Program of Xinjiang Production and Construction Corps
• 2020CB015 Youth Science and Technology Innovation Leading Talents Project of Xinjiang Production and Construction Corps
• CXBJ201907 Youth Innovation Talents Project of Shihezi University
• 2020-PT330-003 Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences

• Biomarkers
• Immunotherapy
• Liver cancer
• Molecular targeted therapy
• Omics analysis

• Humans
• Prospective Studies
• Liver Neoplasms
• Prognosis
• Biomarkers, Tumor
• Tumor Microenvironment

• Circ-EGFR
• Glioma
• MiR-183-5p
• TUSC2

• Animals
• Cell Line, Tumor
• Cell Proliferation
• ErbB Receptors
• Gene Expression Regulation, Neoplastic
• Glioma
• Humans
• Mice
• MicroRNAs
• RNA, Circular
• Tumor Suppressor Proteins

• 81872049 National Natural Science Foundation of China

Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients.

A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta‐analysis.

Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68–2.34) and disease/progression/recurrence‐free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85–2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40–0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28–0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively.

CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

• circular RNA
• diagnosis
• meta-analysis
• prognosis
• renal cell carcinoma

• COL4A1
• Circ_0088364
• HCC
• miR-1270

• Circ_0091579
• Hepatocellular carcinoma
• PLCB1
• miR-1225-5p

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as important posttranscriptional gene and protein expression regulators in cancer. The study goal was to examine VEGFA (vascular endothelial growth factor A) expression in hepatocellular carcinoma (HCC) cell lines upon transfection miR-612, miR-637, or miR-874. Methods: MiR-612 mimics, miR-637 mimics, or miR-874 inhibitors were transfected using Lipofectamine RNAiMax in both HCC cell lines, HepG2 and HuH-7. Real-time PCR, Western blotting, and ELISA methods were used to evaluate VEGFA regulation by the miRNAs. Results: Gene and protein expression levels of VEGFA were down-expressed in both cell lines, HepG2 and HuH-7, transfected with miR-612 or miR-637. Transfection with miR-874 inhibitor showed an increase in VEGFA gene expression in HepG2 and HuH-7 cell lines; however, no regulation was observed on VEGFA protein expression by miR-874 inhibition. Correlation analysis between miRNAs and VEGFA protein expression showed that miR-637 and miR-874 expression present inversely correlated to VEGFA protein expression. Conclusions: VEGFA was down-regulated in response to hsa-miR-612 or hsa-miR-637 overexpression; however, the modulation of VEGFA by miR-874 was observed only at the gene expression and thus, needs further investigation.

• AKT/ERK signal pathway
• Circular RNA
• DYNC1I1
• GPM6A
• circCCNB1
• hepatocellular carcinoma
• miR-106b-5p

• Animals
• Apoptosis
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Caspases/metabolism
• Cell Line, Tumor
• Cell Movement/physiology
• Female
• Hepatitis B/genetics
• Hepatitis B/pathology
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Mice
• Mice, Nude
• MicroRNAs/genetics
• Neoplasm Proteins/metabolism
• RNA, Circular/genetics
• Repressor Proteins/metabolism
• Xenograft Model Antitumor Assays

• AKT/mTOR
• Circ_0007059
• Hepatocellular carcinoma
• PTEN

• Carcinogenesis
• Carcinoma, Hepatocellular/pathology
• Cell Proliferation
• Humans
• Liver Neoplasms/pathology
• MicroRNAs/physiology
• PTEN Phosphohydrolase/physiology
• Proto-Oncogene Proteins c-akt/physiology
• Signal Transduction
• TOR Serine-Threonine Kinases/physiology

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. According to the research of circular RNAs in the CRC field, compared with linear RNAs, circular RNAs are a special type of noncoding RNA that are covalently closed circular structures, which have no 5' cap structure and 3' polyA tail and are not affected by RNA exonuclease and actinomycin D.

Notably, circular RNAs have a high degree of stability and potential effect on gene regulation. Meanwhile, circular RNAs are involved in the sponge action of microRNAs and mediate protein translation and direct binding, alternative splicing, and histone modification.

Studies have shown that circular RNAs are related to the proliferation, invasion, recurrence, metastasis, ferroptosis, apoptosis, and chemotherapy resistance of CRC.

This article provides a brief review based on the source, structural characteristics, mechanisms, biological functions of circular RNAs, and the relationships between CRC.

• biomarker
• cancer stem cell
• circular RNA
• colorectal cancer
• recurrence and metastasis
• therapeutic target

• Biogenesis
• Characteristics
• CircRNAs
• Functions
• Liver cancer
• Mechanisms

• Animals
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• MicroRNAs/genetics
• Neoplasm Invasiveness/genetics
• Neoplasm Invasiveness/pathology
• RNA, Circular/genetics
• Transcriptome

• aquaculture
• biomarker
• circRNA
• growth
• immunity
• myogenesis
• selective breeding

• Circ-CSPP1
• HCC
• HMGB1
• miR-493-5p

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and carries high morbidity and mortality. Diagnosing HCC at an early stage is challenging. Therefore, finding new, highly sensitive and specific diagnostic biomarkers for the diagnosis and prognosis of HCC patients is extremely important. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed loop structures. They are characterized by remarkable stability, long half-life, abundance and evolutionary conservation. Recent studies have shown that many circRNAs are expressed aberrantly in HCC tissues and have important regulatory roles during the development and progression of HCC. Hence, circRNAs are promising biomarkers for the diagnosis and prognosis of HCC. This review: (i) summarizes the biogenesis, categories, and functions of circRNAs; (ii) focuses on current progress of dysregulated expression of circRNAs in HCC with regard to regulation of the tumor hallmarks, “stemness” of cancer cells, and immunotherapy; (iii) highlights circRNAs as potential biomarkers and therapeutic targets for HCC; and (iv) discusses some of the challenges, questions and future perspectives of circRNAs research in HCC.

• biomarker
• circular RNA
• diagnosis
• hepatocellular carcinoma
• prognosis

• biomarkers
• colorectal cancer
• diagnosis
• mRNA
• ncRNA
• prognosis

Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness.

Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells.

miR-145 directly targeted the PD-L1 3′-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues.

Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.

• 0,003,288
• Circ
• EMT
• Hepatocellular carcinoma
• Hsa
• MiR-145
• PD-L1

Circular RNAs (circRNAs) could interact with miRNAs to regulate gene expression, participating in hepatocellular carcinoma (HCC) initiation and development. This work aimed to determine the potential function and molecular mechanism of circEPB41L2 (hsa_circ_0077837) during HCC progression.

The expression of circEPB41L2 in HCC tissues and HCC cell lines was quantified using real-time quantitative PCR (qRT-PCR). CCK-8 assays and colony formation assays were utilized to detect the proliferation of HCC cells. Wound healing assay and transwell assay were performed to determine the capability of migration and invasion for HCC cells. Western blot was conducted to determine gene expression on protein levels. The effect of circEPB41L2 on HCC in vivo was investigated via xenograft experiment. Interaction between circEPB41L2 and miR-590-5p was predicted through bioinformatics methods and confirmed via luciferase reporter assay.

Extensive analysis of circRNA profiles in tumor and matched para-tumor tissues collected from 61 HCC patients identified that circEPB41L2 was significantly down-regulated in HCC, which was further confirmed in another HCC group by qRT-PCR analysis. The clinicopathological analysis revealed that down-regulation of circEPB41L2 was negatively associated with tumor size, vascular invasion and alpha-fetoprotein, while positively correlated with HCC prognosis. The biological function experiments showed that overexpression of circEPB41L2 could obviously inhibit the proliferation and metastasis of HCC cells in vitro, while knockdown of circEPB41L2 induced opposite results. Moreover, we also found that circEPB41L2 inhibited HCC migration and invasion though EMT signaling pathway. Similarly, overexpression of circEPB41L2 can also significantly inhibit the proliferation of HCC cells in vivo. Bioinformatic analysis and luciferase reporter assay revealed that circEPB41L2 interacts directly with miR-590-5p and the corresponding biological functions were also verified in miRNA rescue experiments.

Our results suggest that circEPB41L2 might function as a tumor suppressor during HCC progression by sponging miR-590-5p.

• circEPB41L2
• circular RNA
• hepatocellular carcinoma
• miR-590-5p

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has high mortality. Biomarkers related to HCC, such as alpha-fetoprotein, and imaging technology, such as ultrasound and computed tomography, have been used to screen and monitor HCC, but HCC is still difficult to diagnose effectively in the early stage due to the low sensitivity of the above mentioned traditional methods. There is an urgent need for noninvasive biomarkers to facilitate the screening and early diagnosis of HCC. With the advancement of next-generation sequencing, genetic biomarkers are becoming the core of cancer diagnosis. Genetic biomarkers such as peripheral blood circulating tumor DNA, microRNAs, long noncoding RNAs, circular RNAs, and exosomes have become the focus of early HCC diagnostics. HCC genetic biomarkers have been implemented in clinical practice. In this review, we describe the available literature on peripheral blood genetic biomarkers in the diagnosis of early HCC.

• biomarkers
• exosome
• hepatocellular carcinoma
• microRNA
• nucleic acid

• Alpha-fetoprotein
• Hepatocellular carcinoma
• Hyperspectral imaging
• Laser pointer
• RNA folding
• Remote sensing
• Smartphone CCD camera
• Spectral signature
• Transcriptomes

• MAPK pathway
• MicroRNA
• ameloblastoma
• circular RNA
• odontogenic tumor

Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR‐660 while miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR‐660, which resulted in an upregulated expression of BAG5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR‐660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305‐mediated miR‐660‐5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression.

• BAG5
• circ_0008305
• hepatocellular carcinoma
• miR-660

Circular RNAs (circRNAs) represent a distinct class of non-coding RNAs that have attracted substantial research attention in recent years. We identified a novel circRNA derived from golgi glycoprotein 1 mRNA (circ_GLG1), the role of which is unknown in colorectal cancer (CRC). The purpose of this study was to explore the potential roles and mechanisms of circ_GLG1 in CRC.

Quantitative reverse transcriptase-polymerase chain reaction analysis was performed to quantify circ_GLG1 expression in 40 pairs of CRC tissues and adjacent normal tissues as well as CRC cell lines. DLD1 CRC cells were transfected with a small-interfering RNA against circ_GLG1, after which cell proliferation, viability, invasion, and migration were measured through cell counting kit-8 colony-formation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter assays were performed to explore the binding sites among circ_GLG1, miR-622, and Kirsten rat sarcoma (KRAS) transcripts. KRAS protein expression was detected using Western blot analysis.

Circ_GLG1 expression was significantly higher in CRC tissues than in adjacent normal tissues. Knocking down circ_GLG1 in DLD1 cells inhibited tumor cell viability, proliferation, invasion, and migration, and these effects were reversed by co-transfecting an miR-622 inhibitor. Circ_GLG1 promoted KRAS expression at both the mRNA and protein levels by acting as an miR-622 sponge. Dual-luciferase reporter assays demonstrated that miR-622 interacted with circ_GLG1 and KRAS mRNA.

Our study revealed the role of the circ_GLG1–miR-622–KRAS axis in CRC. Moreover, our findings provide insight into the molecular mechanism of circ_GLG1 in CRC and suggest potential new biomarkers for diagnosing this disease.

• KRAS
• circ_GLG1
• colorectal cancer
• miR-622

There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism.

The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay and Spearman correlation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells.

CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC.

CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p.

• CircSMYD4
• Circular RNA
• Hepatocellular carcinoma
• Proliferation
• miR-584-5p

• CAB39
• QKI
• circGSK3B
• glutaminolysis
• hepatocellular carcinoma
• miR-1265

Hepatocellular carcinoma (HCC) is a common lethal malignant tumor worldwide. Circular RNAs (circRNAs) have been reported to affect the development of human cancers, including HCC. In this project, we aim to clarify the functional effect of circular CDR1as (circ_CDR1as) on HCC progression.

Quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot is implemented to detect the expression of circ_CDR1as, microRNA (miR)-1287 and Raf-1 proto-oncogene, serine/threonine kinase (Raf1). Cell proliferation is assessed via colony formation and 3-(4, 5)-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide (MTT) assays. Cell migration and invasion are measured by Transwell assay. The target relationship between miR-1287 and circ_CDR1as or Raf1 is validated through dual-luciferase reporter assay. The levels of epithelia–mesenchymal transition (EMT) markers and the MEK/ERK signal pathway-related proteins are examined by Western blot. Model in nude mice is constructed to determine the role of circ_CDR1as in vivo.

Expression of circ_CDR1as and Raf1 is elevated, while miR-1287 expression is decreased in HCC. Depletion of circ_CDR1as or Raf1 could inhibit proliferation and metastasis of HCC cells. Besides, circ_CDR1as regulates Raf1 expression by targeting miR-1287. MiR-1287 upregulation or Raf1 depletion could partially counterbalance circ_CDR1as depletion-mediated inhibitory effects on HCC cell behaviors. Moreover, circ_CDR1as depletion represses HCC progression through inactivating MEK/ERK pathway. In addition, circ_CDR1as depletion suppresses tumor growth in vivo via regulating miR-1287/Raf1 pathway.

Circ_CDR1as depletion inhibits HCC cell proliferation and metastasis by miR-1287/Raf1 and MEK/ERK pathways, highlighting a promising molecular target for HCC treatment.

• HCC
• MEK/ERK pathway
• Raf1
• circ_CDR1as
• metastasis
• miR-1287
• proliferation

Although accumulating documents have expounded the pivotal position of circular RNAs (circRNAs) in hepatocarcinogenesis and progression, the overwhelming majority of their functions and molecular mechanisms in hepatocellular carcinoma (HCC) are elusive. Herein, we explored the functions and potential mechanisms of hsa_circ_0005785 in HCC, which was aberrantly overexpressed in HCC and related to HCC patients' TNM stage and overall survival. Moreover, hsa_circ_0005785 depletion could repress proliferation and metastasis of the HCC cell in vitro, lead to cell apoptosis and cell-cycle arrest, and restrain HCC cell growth in vivo. Furthermore, mechanism analyses discovered that hsa_circ_0005785 adsorbed miR-578 by playing a miRNA sponge role, which resulted in the derepression of a proliferation-inducing ligand (APRIL) expression, miR-578's mRNA target. Besides, hsa_circ_0005785 reversed the suppressive influence of miR-578 on HCC and accelerated tumor malignant progression through the miR-578/APRIL axis. Taken together, our current study revealed an oncogenic role of hsa_circ_0005785 in the tumorigenesis of HCC. Moreover, targeting to the hsa_circ_0005785/miR-578/APRIL regulatory pathway might be a promising diagnostic and therapeutic strategy for HCC clinical practice.

• APRIL
• circular RNA
• hepatocellular carcinoma
• hsa_circ_0005785
• miR-578

Recently, studies have demonstrated that a novel circular RNA (circRNA), circMAT2B, can promote cell proliferation and can thus contribute to the growth and development of hepatocellular carcinoma. However, the precise mechanisms underlying in circMAT2B-induced colorectal cancer (CRC) cell proliferation are not yet fully understood.

Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circMAT2B expression in 70 CRC tissues and 70 matched adjacent normal tissues, CRC cell lines and human colonic epithelial cell line (NCM460). The direct interaction between miR-610 and circMAT2B or E2F1 was verified using luciferase reporter assay and biotinylated RNA Pull-down assay. Cell Counting Kit-8, colony formation assay, flow cytometry were utilized to examine the effect of circMAT2B, miR-610 and E2F1 on cell proliferation. Western blot was conducted to evaluate E2F1 expression.

In our study, circMAT2B was found to be upregulated in CRC tissues and cell lines. Furthermore, the silencing of circMAT2B significantly inhibited proliferation. Hence, in order to investigate the mechanism underlying the oncogenic properties of circMAT2B in CRC, a bioinformatics analysis (circular RNA Interactome, https://circinteractome.nia.nih.gov/) was performed to screen the putative interacting microRNAs of circMAT2B. miR-610 was identified to be one of the potential targeted miRNAs of circMAT2B. Luciferase reporter and RNA pulldown assay confirmed a direct interaction between circMAT2B and miR-610. Moreover, circMAT2B expression was negatively correlated with the expression of miR-610 in CRC tissues (r=−0.5131, p<0.0001). Furthermore, we demonstrated circMAT2B upregulated expression levels of the miR-610 target gene E2F1, which is involved in cell proliferation, is overexpression in a broad range of human cancer including CRC. Further studies suggested that E2F1 upregulation could significantly reverse the si-circMAT2B-mediated inhibition of proliferation.

circMAT2B is upregulated in CRC tissues and cell lines. Moreover, circMAT2B promoted CRC proliferation by regulating the miR-610/E2F1 axis, which may serve as a potential therapeutic target for CRC treatment.

• E2F1
• circMAT2B
• colorectal cancer
• miR-610
• proliferation

Many studies have confirmed that circular RNAs (circRNAs) play a key role in the biological progression of cancers. However, the function of a novel circRNA, circ_0046599, in hepatocellular carcinoma (HCC) progression has not been explored.

Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of circ_0046599, microRNA (miR)-1258 and Ribophorin II (RPN2). Subcellular fractionation location assay was used to localize circ_0046599 in HCC cells. The circular characteristic of circ_0046599 was verified using Ribonuclease R (RNase R) digestion assay. Besides, cell counting kit 8 (CCK8) assay, colony formation assay, wound healing assay and transwell assay were used to detect cell proliferation, migration and invasion, respectively. The lactate production and glucose level were determined by Lactate and Glucose Assay Kits. Furthermore, the protein levels of glycolysis, metastasis and proliferation-related marker proteins, as well as RPN2 were tested by Western blot (WB) analysis. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to confirm the interactions among circ_0046599, miR-1258 and RPN2. In addition, mice xenograft models were applied to observe the effect of circ_0046599 silencing on HCC tumor growth in vivo.

Circ_0046599 was highly expressed in HCC tissues and cells, and its knockdown could suppress HCC cell proliferation, migration, invasion and glycolysis process. MiR-1258 could be targeted by circ_0046599, and its inhibitor could invert the suppressing effect of circ_0046599 knockdown on HCC progression. Further, RPN2 was a target of miR-1258. Overexpressed RPN2 could reverse the inhibiting effect of miR-1258 overexpression on HCC progression. Also, knockdown of circ_0046599 could restrain HCC tumor growth in vivo.

Our results provided new evidence that circ_0046599 could promote the progression of HCC by increasing RPN2 expression via sponging miR-1258.

• HCC
• RPN2
• circ_0046599
• miR-1258
• progression

• Circular RNA
• Exosome
• Hepatocellular carcinoma

• Aged
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/surgery
• Case-Control Studies
• Disease-Free Survival
• Exosomes/metabolism
• Female
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasm Recurrence, Local/epidemiology
• Prognosis
• Proto-Oncogene Proteins c-akt/genetics
• RNA, Circular/metabolism

• Circ_0001178
• Hepatocellular carcinoma
• VEGFA
• miR-382

Circular RNA (circRNA) is an intriguing class of RNA with covalently closed-loop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.

• biomarker
• cancer
• circRNA
• gene splicing and transcription
• miRNA sponge
• protein scaffolding
• therapeutic target

• hepatectomy
• hepatocellular carcinoma
• mean corpuscular hemoglobin concentration
• overall survival
• recurrence-free survival

• HuR
• cell cycle
• circRNAs
• hepatocellular carcinoma
• p27

Circular RNAs (circRNAs) are a class of newly discovered RNAs that attach great importance to modulate gene expression and biological function. Nonetheless, in gastric cancer (GC), the expression and function of circRNA are much less explored. In this study, circ_0000267 expression in GC was investigated and the function and mechanism of circ_0000267 was probed.

Quantitative real‐time PCR (qRT‐PCR) was employed to detect circ_0000267, miR‐503‐5p, and HMGA2 expression. Immunohistochemistry and western blot were adopted to detect HMGA2 and epithelial–mesenchymal transition (EMT)‐related proteins (E‐cadherin and N‐cadherin) expression in GC tissues and cells, respectively. GC cell lines with circ_0000267 overexpressed and knocked down were constructed, and CCK‐8 assay, BrdU assay, scratch healing assay, and transwell assay were employed to assess the effect of circ_0000267 on the proliferation and metastasis of GC cells. Besides, dual‐luciferase reporter gene assay was adopted to verify the targeting relationship between circ_0000267 and miR‐503‐5p.

Circ_0000267 showed a significant upregulation in GC tissues and cell lines, and its high expression level was extremely linked to the increased tumor diameter and local lymph node metastasis. Circ_0000267 overexpression accelerated GC cell proliferation, metastasis, and EMT processes, while knocking down circ_0000267 led to the opposite effect. From the perspective of mechanism, circ_0000267 promoted the progression of GC through adsorbing miR‐503‐5p and upregulating HMGA2 expression.

Circ_0000267 is an oncogenic circRNA that affects the progression of GC, which participates in promotion of GC proliferation, migration, invasion, and EMT via modulating the miR‐503‐5p/HMGA2 axis.

• HMGA2
• Gastric cancer
• circ_0000267
• miR-503-5p

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs that may have roles in cancer genesis and development. In the recent literature, dysregulated circRNAs have been extensively investigated in hepatocellular carcinoma (HCC). Whether or not circRNAs are of clinical value for the management of HCC has not been characterized.

To meta-analyze the diagnostic and prognostic value of abnormally expressed circRNAs in HCC.

Eligible studies were sourced from PubMed, EMBASE, and CNKI online databases. Data on patients’ clinical characteristics, including diagnostic efficacy and overall survival, were extracted. The diagnostic and prognostic parameters were respectively synthesized using the bivariate meta-analysis model and multivariate Cox hazard regression analysis based on Stata 12.0. The trim and fill method was adopted to assess the possible effects from publication bias.

A total of 21 eligible studies were included. The pooled sensitivity, specificity, and area under the curve of abnormally expressed circRNAs in distinguishing HCC from non-cancer controls were 0.78 (95%CI: 0.69–0.85), 0.80 (95%CI: 0.74–0.86), and 0.86, respectively. Survival analyses showed that the down-regulated circRNA expression signature correlated perfectly with HCC survival [hazard ratio (HR) = 0.42, 95%CI: 0.19–0.91, P = 0.028; I² = 92.7%, P = 0.000], whereas the HCC cases with high circRNA levels had significantly poorer prognoses than those of patients with low circRNA levels (HR = 2.22, 95%CI: 1.50–3.30, P = 0.000; I² = 91%, P = 0.000). Moreover, abnormally expressed circRNAs were intimately associated with tumor size, differentiation grade, microvascular invasion, metastasis, TNM stage, and serum alpha fetal protein level in patients with HCC. Stratified analysis based on sample type, control source, and expression status also yielded robust results.

Abnormally expressed circRNA signatures show immense potential as novel non-invasive biomarker(s) for HCC diagnosis and prognosis.

• CircRNA
• Hepatocellular carcinoma
• Diagnosis
• Prognosis
• Meta-analysis

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a leading cause of cancer-related deaths worldwide. Emerging studies have shown that circular RNAs (circRNAs) are differentially expressed in HCC and play an important role in HCC pathogenesis and metastasis. However, the mechanism of circRNA in the chemoresistance of HCC remains unclear. In this study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We identified a novel circRNA circRNA_101505 that was decreased in cisplatin-resistant HCC tissues and cell lines, and associated with a poor survival outcome. Gain-of-function investigations showed that overexpression of circRNA_101505 suppressed cancer cell growth in vivo and in vitro, and enhanced cisplatin toxicity in HCC cells. Mechanistic studies found that circRNA_101505 could sensitize HCC cells to cisplatin by sponging miR-103, and thereby promoting oxidored-nitro domain-containing protein 1 (NOR1) expression. In conclusion, the significant inhibitory effects indicate circRNA_101505 to be a potential therapeutic target for HCC treatment. Our findings provide significant evidence to further elucidate the therapeutic use of circRNA in HCC.

• Cancer therapy
• Tumour-suppressor proteins

Circular RNAs (circRNAs) play important roles in the progression of cancers, but the precise role of circRNAs in the diagnosis and prognosis of hepatocellular carcinoma (HCC) remains to be clarified. The aim of the current study was to explore the diagnostic and prognostic values of hsa_circ_0003998 in HCC.

CircRNAs expression was measured using RNA-seq analysis from HCC tissues (n=6) (three cases with or without portal vein invasion). Hsa_circ_0003998 in 200 pairs of HCC and adjacent noncancerous tissues and HCC cell lines was examined using qRT-PCR and the clinicopathologic significance was determined. We also detected the plasma levels of hsa_circ_0003998 in HCC, hepatitis B patients and healthy controls. The clinical diagnosis and prognostic values were further determined using receiver operating characteristic (ROC) curve, Kaplan–Meier curve and Cox regression.

Hsa_circ_0003998 was upregulated in HCC tissues (P<0.001) and HCC cell lines (HepG2, HuH7, MHCC97H) (P<0.001). In addition, upregulation of hsa_circ_0003998 level was associated with higher serum alpha-fetoprotien (AFP) level (P=0.003), larger tumor diameter (P=0.009), lower differentiation level (P=0.023) and microvascular invasion (P=0.028). The plasma level of hsa_circ_0003998 in HCC patients was significantly higher than those in hepatitis B patients (P<0.001) and healthy controls (P<0.001). Its level was significantly reduced after the operation (P<0.001). The area under the ROC curve (AUC) for distinguishing HCC from adjacent noncancerous tissues was 0.894 (95% CI=0.86–0.922, P<0.001), the sensitivity and specificity were 0.84 and 0.8, respectively. Comparing with hepatitis B patients and healthy controls, hsa_circ_0003998, respectively, had an AUC value of 0.833 (95% CI=0.763–0.889, P<0.001) and 0.892 (95% CI=0.831–0.937, P<0.001). Their sensitivity and specificity were 0.83, 0.7 and 0.8, 0.84, respectively. Moreover, the combination of hsa_circ_0003998 and AFP showed the highest AUC value of 0.947, the sensitivity and specificity were 0.88 and 0.92, respectively. The hsa_circ_0003998 (P=0.003) and AFP (P=0.008) levels were independent prognostic factors for HCC. The overall survival of HCC patients with high level of hsa_circ_0003998 was significantly poorer than those with low level (P=0.005).

Our findings suggest that hsa_circ_0003998 may be used as a novel potential biomarker for the diagnosis and prognosis of HCC patients.

• biomarker
• circular RNA
• diagnosis
• hepatocellular carcinoma
• hsa_circ_0003998
• prognosis

Epithelial cell adhesion molecule (EpCAM) is highly expressed during liver development and carcinogenesis, However, its functions and underlying mechanisms remain unclear. Clustered regularly interspaced short palindromic repeats (CRISPRs)/CRISPR-associated protein 9 (Cas9) technology was used in the current study to establish EpCAM^−/− mice. The expression of EpCAM in the livers of the mice at embryonic day (E)18.5 and post-natal day (P)0 was detected by immunofluorescence staining. The expression of genes associated with the development and glycogen metabolism was also assessed by reverse transcription-quantitative PCR. Additionally, the liver tissue of the EpCAM^−/− and wild-type mice was used for non-coding RNA sequencing. The results of RNA sequencing revealed 11 up-regulated and 12 downregulated circular RNAs (circRNAs). Kyoto Encyclopedia of Genes and Genomes analysis for resource genes determined that the top altered pathways included cell junctions, cell cycle, immune signaling and metabolism. This analysis was also utilized to predict the target association of the circRNA-microRNA-mRNA network. The comprehensive liver tissue circRNA expression profiles produced in the present study may help to elucidate the functions and mechanisms of EpCAM during liver development.

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs. Owing to the development of high-throughput sequencing, researchers have identified thousands of circRNAs. Emerging evidence suggests that circRNAs are involved in various tumor cell processes, including proliferation, apoptosis, invasion and migration. Because of their high stability and abundance, tissue-specific expression, and easy detection, circRNAs are considered ideal biomarkers for cancer diagnosis and prognosis. An increasing number of studies have recently demonstrated that circRNAs are closely associated with colorectal cancer (CRC). CRC is the third most common cancer and the second leading cause of cancer-related death globally. Thus, understanding the molecular mechanisms involved in the development and progression of CRC is vital. In this review, we summarize the current literature regarding human circRNAs related to CRC and present an overview of the potential clinical implications of circRNAs with respect to CRC.

• biomarker
• circRNA
• diagnosis
• prognosis

• circ-POSTN
• circular RNA
• glioma
• miR-1205

Worldwide, bladder cancer represents the ninth most common malignancy and is the 13^th cause of cancer-associated death. Although surgery combined with chemotherapy and radiotherapy has improved patient outcomes, the prognosis remains poor for most patients with muscle-invasive bladder cancer. The exact mechanisms and critical regulators of bladder cancer remain unknown. Circular RNAs (circRNAs) are a distinct type of endogenous non-coding RNA. Recent studies have shown that circRNAs participate in many processes, including proliferation, invasion, migration, and apoptosis in multiple types of malignancy, including bladder cancer. Some circRNAs are dysregulated in bladder cancer and play essential roles in cancer progression. Importantly, some circRNAs may serve as diagnostic and prognostic biomarkers for bladder cancer. This review aims to summarize the findings from recent studies that have focused on the roles of human circRNAs in bladder cancer and discusses the clinical roles for circRNAs, including their potential roles as diagnostic or prognostic biomarkers.