circRNA has been established to play a pivotal role in tumorigenesis development in a variety of cancers; nevertheless, the biological functions and molecular mechanisms of hypoxia-induced exosomal circRNAs in pancreatic cancer remain largely unknown.Differentially expressed circRNAs in exosomes between hypoxic exosomes and normoxic exosomes in PC cells were verified by RNA sequencing. The expression of circPDK1 in PC tumors and PC patients was evaluated by qRT-PCR and ISH, and the biological functions of circPDK1 in PC were verified through a series of in vitro and in vivo experiments. Using Western blotting, Co-IP, RNA pull-down, ChIP, RIP, dual-luciferase assays, and rescue experiments, the underlying mechanism of circPDK1 was verified.CircPDK1 was highly abundant in PC tumor tissues and serum exosomes and was associated with poor survival. Exosomal circPDK1 significantly promoted PC cell proliferation, migration, and glycolysis both in vitro and in vivo. Mechanistically, circPDK1 could be activated by HIF1A at the transcriptional level and sponges miR-628-3p to activate the BPTF/c-myc axis. In addition, circPDK1 serves as a scaffold that enhances the interaction between UBE2O and BIN1, inducing the UBE2O-mediated degradation of BIN1.We found that circPDK1 was activated by HIF1A at the transcriptional level by modulating the miR-628-3p/BPTF axis and degrading BIN1. Exosomal circPDK1 is a promising biomarker for PC diagnosis and prognosis and represents a potential therapeutic target for PC. 

/pdf/hypoxia-induced-exosomal-circpdk1-promotes-pancreatic-cancer-2clhllju.pdf

Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1

Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights.

A new class of noncoding RNAs, tsRNAs are not only abundant in humans but also have high tissue specificity. Recently, an increasing number of studies have explored the correlations between tsRNAs and tumors, showing that tsRNAs can affect biological behaviors of tumor cells, such as proliferation, apoptosis and metastasis, by modulating protein translation, RNA transcription or posttranscriptional regulation. In addition, tsRNAs are widely distributed and stably expressed, which endows them with broad application prospects in diagnosing and predicting the prognosis of tumors, and they are expected to become new biomarkers. However, notably, the current research on tsRNAs still faces problems that need to be solved. In this review, we describe the characteristics of tsRNAs as well as their unique features and functions in tumors. Moreover, we also discuss the potential opportunities and challenges in clinical applications and research of tsRNAs. 

Biological functions and clinical significance of tRNA-derived small fragment (tsRNA) in tumors: Current state and future perspectives.

Circular RNAs are single-stranded RNAs with a covalently closed structure formed by the process of back-splicing. Aberrant expression of circular RNAs contributes to the pathogenesis of a wide range of cancers. Pancreatic cancer is one of the most lethal cancers due to diagnostic difficulties and limited therapeutic options. Circular RNAs are emerging as novel diagnostic biomarkers and therapeutic targets for pancreatic cancer. Moreover, recent advances in the therapeutic application of engineered circular RNAs have provided a promising approach to overcoming pancreatic cancer. This review discusses the roles of circular RNAs in the pathogenesis of pancreatic cancer and in potential treatment applications and their usefulness as diagnostic biomarkers.

/pdf/roles-of-circular-rnas-in-the-pathogenesis-and-treatment-of-1tshz0bn.pdf

Roles of circular RNAs in the pathogenesis and treatment of pancreatic cancer

ABSTRACT Background Gastric cancer (GC) is one of the most common types of cancer worldwide. Recent studies have shown that tsRNAs play important roles in GC and that changes in the expression levels of tsRNAs can be used for GC diagnosis and treatment response prediction. Research design and methods Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the correlation between tsRNA expression and prognosis and other clinicopathologic features of GC patients. The sensitivity, specificity, area under the receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were analyzed to evaluate the diagnostic value of tsRNAs. Results The results showed that patients with tsRNA upregulation had a poor prognosis (HR = 2.48, 95% CI: 1.85–3.34), while patients with tsRNA downregulation had a favorable prognosis (HR = 0.55, 95% CI: 0.31–0.98). In addition, tsRNA expression was significantly correlated with various clinicopathological features in patients with GC. Finally, in diagnostic studies, GC-related tsRNAs could differentiate healthy controls (AUC = 0.81, DOR = 7.74) from patients with inflammation (AUC = 0.74, DOR = 4.44). Conclusions tsRNAs have potential clinical application in GC diagnosis and prognosis evaluation. It is necessary to further assess and verify the practicability and feasibility of additional specific tsRNAs as GC markers in the future.

The diagnostic and prognostic value of tsRNAs in gastric cancers: a systematic review and meta-analysis

Pancreatic cancer (PC) is a highly malignant solid tumor with insidious onset and easy early metastasis. Despite tremendous efforts devoted to research in this field, the mechanisms underlying PC tumorigenesis and progression remain unclear. Additionally, robust biomarkers and satisfactory therapeutic strategies for clinical use in PC patients are still lacking. Circular RNAs (circRNAs) are a new type of non-coding RNA originating from precursor messenger RNAs, with a covalent continuous closed-loop structure, strong stability and high specificity. Accumulating evidence suggests that circRNAs may participate in PC development and progression. Abnormal expression of circRNAs in PC is considered a vital factor that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis and drug resistance. In this review of relevant articles published in recent years, we describe the basic knowledge concerning circRNAs, including their classification, biogenesis, functions and research approaches. Moreover, the biological roles and clinical significance of circRNAs related to PC are discussed. Finally, we note the questions remaining from recent studies and anticipate that further investigations will address these gaps in knowledge in this field. In conclusion, we expect to provide insights into circRNAs as potential targets for specific PC diagnosis and treatment in the future. 

/pdf/biological-functions-mechanisms-and-clinical-significance-of-3j0s7rw1.pdf

Biological functions, mechanisms, and clinical significance of circular RNA in pancreatic cancer: a promising rising star

/pdf/biological-functions-mechanisms-and-clinical-significance-of-1eo21qqe.pdf

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Biological functions, mechanisms, and clinical significance of circular RNA in pancreatic cancer: a promising rising star

Biological functions, mechanisms, and clinical significance of circular RNA in pancreatic cancer: a promising rising star