Exosomes are nano-sized membrane-bound vesicles and contain active substances (DNA, noncoding RNA [ncRNA], protein), which provide a novel method of transferring effector messages between cells. Circular RNAs (circRNAs), a kind of ncRNA, have attracted increasing attention over the last decade given advances in whole-genome and transcriptome sequencing technologies. It has become increasingly clear that circRNAs regulate gene expression through various actions and play diverse roles in many fields of human cancer biology. Notably, several studies reported that circRNAs are enriched in exosomes and that exosomal circRNAs play an important role in cancer biology. Exosomal circRNAs can be taken up by neighboring or distant cells and affect many aspects of physiological and pathological conditions of the recipient cells, potentially promoting cell communication and tumor metastasis. Herein, we briefly review the molecular mechanisms of circRNAs and recent findings regarding exosomal circRNAs, and highlight the specific roles of exosomal circRNAs in human cancer.

The colorectal cancer (CRC) is one of the leading causes of cancer‐related death worldwide, but the pathogenesis of CRC remains not well‐known. Increasing studies have highlighted the critical roles of long noncoding RNAs (lncRNAs) in tumorigenesis and cancer cells metastasis, however, the expression pattern, biological roles of lncRNAs, and the mechanisms responsible for their function in CRC remain elusive. In this study, we performed a genome‐wide comprehensive analysis of lncRNAs profiling and clinical relevance to identify novel lncRNAs for the further study in CRC. RNA sequencing and microarray data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were annotated and analyzed to find differentially expressed lncRNAs in CRC. Analysis of these datasets revealed that hundreds of lncRNAs expression are dysregulated in CRC tissues when compared with normal tissues. By genomic variation analyses, we identified that some of these lncRNAs dysregulation is associated with the copy number amplification or deletion. Moreover, many lncRNAs expression levels are significantly associated with CRC patients overall and recurrence‐free survivals, such as H19, LEF1‐AS1, and RP11‐296E3.2. Furthermore, we identified one liver metastasis‐associated lncRNA termed LUCAT1 in CRC by analyzing lncRNAs expression profiles in the CRC tissues from patients with liver metastasis compared with the CRC tissues without metastasis. Finally, loss‐of‐function assays determined that knockdown of LUCAT1 could impair CRC cells invasion. Taken together, aberrantly expressed lncRNAs may play critical roles in the development and liver metastasis of CRC, and our findings may provide useful resource for identification of novel biomarkers of CRC.

Recently, a growing number of evidence has revealed that long noncoding RNAs (lncRNAs) act as key regulators in various cellular biologic processes, and dysregulation of lncRNAs involves in tumorigenesis and cancer progression. However, the expression pattern, clinical relevance, and biologic function of most lncRNAs in human thyroid cancer remain unclear. To identify more thyroid‐cancer‐associated lncRNAs, we analyzed the expression profile of lncRNAs in thyroid cancer tissues and adjacent normal or non‐tumor tissues using RNA sequencing data and gene microarray data from The Cancer Genome Atlas and Gene Expression Omnibus. Annotation and analyses of these data revealed that hundreds of lncRNAs are differentially expressed in thyroid cancer tissues when compared with normal tissues. By copy number variation analyses, we identified that some of those dysregulated lncRNAs genome locus are accompanied with the copy number amplification or deletion. Moreover, some lncRNAs expression levels are significantly associated with thyroid cancer patients overall or recurrence‐free survival time, such as RUNDC3A‐AS1, FOXD2‐AS1, PAX8‐AS1, and CRYM‐AS1. Furthermore, we validated an lncRNA termed LINC00704 in thyroid cancer cells by performing loss of function assays. Downregulation of LINC00704 could significantly impair thyroid cancer cells proliferation, colony formation, inhibit cell‐cycle progression and cell invasion, and induce cell apoptosis. Taken together, our findings reveal that lots of lncRNAs are dysregulated and may play critical roles in thyroid cancer, and this study could provide useful resource for identification and investigation of novel lncRNA candidates for thyroid cancer.

Background and aimLong non-coding RNAs (lncRNAs) are implicated as novel factors in tumorigenesis and tumor progression. Although thousands of lncRNAs have been discovered, only a small portion have been functionally determined in hepatocellular carcinoma (HCC). Here, we aimed to comprehensively analyze differentially expressed lncRNAs, evaluate their clinical significance, and explore the functional roles and underlying mechanism in HCC.MethodsWe identified hundreds of lncRNAs which were dysregulated in HCC tissues through performing integrative analyses using the RNA sequencing data and independent gene microarray data from Gene Expression Omnibus and the Cancer Genome Atlas.ResultsDysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. Further experimental validation revealed that down-regulation of lncRNA DUXAP8 inhibited HCC cells proliferation and colony formation ability. Mechanistically, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with histone-lysine N-methyltransferase enzyme enhancer of zeste homolog 2.ConclusionTaken together, our findings can provide a valuable resource of HCC-associated lncRNAs and new insights into the biological functions of lncRNAs in HCC development.

BackgroundRecently, the pesudogenes have emerged as critical regulators in human cancers tumorigenesis and progression, and been identified as a key revelation in post-genomic biology. However, the expression pattern, biological function and mechanisms responsible for these molecules in human gastric cancer (GC) are not fully understood.MethodsIn this study, we globally assessed the transcriptomic differences of pesudogenes in gastric cancer using publicly available microarray data. DUXAP10 expression levels in GC tissues and cells was detected using quantitative real-time PCR (qPCR). DUXAP10 siRNAs and over-expression vector were transfected into GC cells to down-regulate or up-regulate DUXAP10 expression. Loss- and gain-of function assays were performed to investigate the role of DUXAP10 in GC cells cell proliferation, and invasion. RIP, RNA pulldown, and ChIP assays were used to determine the mechanism of DUXAP10’s regulation of underlying targets.ResultsThe pesudogene DUXAP10 is the only pseudogene that significantly over-expressed in all four GEO datasets, and frequently over-expressed in many other cancers including Liver Hepatocellular carcinoma, Bladder cancer, and Esophageal Cancer. High DUXAP10 expression is associated with GC patients poor prognosis, and knockdown of DUXAP10 significantly inhibits cells proliferation, migration and invasion in GC. Mechanistic investigation shows that DUXAP10 can interact with PRC2 and LSD1 to repress LATS1 expression at transcriptional level, and bind with HuR to maintain the stability of β-catenin mRNA and increase its protein levels at post-transcriptional level.ConclusionsOverall, our findings illuminate how increased DUXAP10 confers an oncogenic function in GC development and progression that may serve as a candidate prognostic biomarker and target for clinical management of GC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0684-8) contains supplementary material, which is available to authorized users.

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Recently, a growing number of studies have indicated that long noncoding RNAs (lncRNAs) are emerging as new critical regulators of tumorigenesis and prognostic markers in multiple cancers. However, the expression pattern of lncRNAs and their contributions in renal cell carcinoma (RCC) remains poorly understood. In this study, we performed a genome-wide comprehensively analysis of lncRNAs profiling and clinical relevance to provide valuable lncRNA candidates for the further study in RCC. RCC and non-tumor tissues RNA sequencing data, and microarray data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then, these data were annotated and analyzed to find dysregulated lncRNAs in RCC. We identified that hundreds of lncRNAs were differentially expressed in RCC tissues compared with normal tissues, and genomic variation analyses revealed that copy number amplification or deletion happened in some of these lncRNAs genome loci. Moreover, lots of lncRNAs expression levels are significantly associated RCC patients overall survival time, such as PVT1 and DUXAP8. Finally, we identified some novel metastasis associated lncRNAs in RCC (such as DUXAP8) by analyzing lncRNAs profiling in the RCC tissues from patients with metastasis compared with the primary RCC tissues without metastasis; knockdown of DUXAP8 could impair RCC cells invasive ability in vitro. Overall, our findings illuminate a lot of lncRNAs are aberrantly expressed in RCC that may offer useful resource for identification novel prognostic markers in this disease.

Decorin (DCN), as an important component of the extracellular matrix (ECM), is a small leucine-rich proteoglycan and synthesized by fibroblasts. Although DCN is dysregulated in numerous cancer types, limited data are available on the expression level and important role of DCN proteins in renal cell carcinoma (RCC). In our study, we examined the expression patterns of DCN messenger RNA (mRNA) in RCCs through the Oncomine database and DCN protein in 94 RCC specimens by immunohistochemistry (IHC). The results revealed that DCN expression was decreased in cancerous tissues compared to adjacent noncancerous tissues and was highly correlated to tumor size. Then, via gain-of-function analyses, DCN overexpression could inhibit RCC cell proliferation and metastasis in vitro and vivo. At the mechanism level, we found that an ectopic expression of DCN significantly upregulated P21 and E-cadherin expression. Altogether, these results revealed that DCN is a tumor suppressor in RCC, and it could serve as a potential therapeutic target in patients with RCC.