Circular RNAs (circRNAs) are emerging as cardinal areas of focus in the non-coding RNA field. Growing evidences have revealed exosomal circRNAs as potential biomarkers for detection of various cancers. However, the clinical importance of most serum exosomal circRNAs in colorectal cancer (CRC) have rarely been investigated. In this study, we examined the possible clinical application of serum exosomal circRNAs in the diagnosis of CRC. Firstly, we conducted RNA sequencing (RNA-seq) analysis using fifty CRC and fifty healthy control serum samples to identify CRC-related circRNAs. The sequencing data showed 122 differentially expressed circRNAs including 100 up-regulated and 22 down-regulated circRNA transcripts in CRC patients. Then, eight most dysregulated circRNAs were selected for validation by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Validation analysis revealed that the serum exosomal circ-PNN (hsa_circ_0101802) levels were significantly up-regulated in CRC cases compared with those in the healthy control groups. Receiver operating characteristic curve (ROC) analysis suggested that circ-PNN had significant value in CRC diagnosis with areas under the ROC curve (AUC) of 0.855 and 0.826 in the training and validation sets, respectively. We also found that the AUC of serum exosomal circ-PNN for early-stage CRC was 0.854. Finally, a network map based on circ-PNN was constructed to determine its potential miRNA-mRNAs binding. We also demonstrated that the expression of hsa-miR-6833-3P, hsa-let-7i-3p and hsa-miR-1301-3P were negatively correlated with circ-PNN in CRC patients. Collectively, our findings indicated that serum exosomal circ-PNN might be a potential non-invasive biomarker for the detection of CRC and may play a crucial role in the pathogenesis of CRC.

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Gastric cancer (GC) is a type of cancer that is commonly diagnosed worldwide due to a lack of early diagnostic, prognostic and therapeutic targets for this disease. The aim of the present study was to examine the expression levels of five long non-coding RNAs, namely PTPRG antisense RNA 1 (PTPRG-AS1), forkhead box P4 antisense RNA 1 (FOXP4-AS1), bladder cancer-associated transcript 2 (BLACAT2), ZXF2 and upregulated in colorectal cancer (UCC), to study their associations with patient characteristics and assess their prognostic efficacy, in order to determine the possibility of their application as GC biomarkers. The expression levels of long non-coding RNAs (lncRNAs) were determined by reverse transcription-quantitative PCR analysis of 61 pairs of GC tissues and adjacent healthy gastric mucosa tissues and GC cell lines. The Chi-square test was conducted to assess the associations of lncRNA expression levels with clinical characteristics of patients. The effect of UCC on GC cell proliferation was determined using in vitro functional experiments. The prognostic efficacy of FOXP4-AS1, BLACAT2 and UCC were examined in the Gene Expression Profiling Interactive Analysis database and those of PTPRG-AS1 were examined in the Kaplan Meier Plot database. Gene alteration frequencies of PTPRG-AS1 and BLACAT2 in GC were identified using the cBioPortal for Cancer Genomics. PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC were found to be upregulated in GC cell lines and GC tissues compared with adjacent normal tissues. PTPRG-AS1 and ZXF2 expression levels were associated with the expression status of the cell proliferation marker Ki67. UCC promoted the proliferation of GC cells in vitro and was associated with lymph node metastasis. Increased expression of FOXP4-AS1 indicated a favorable outcome in terms of disease-free survival, whereas high expression of PTPRG-AS1 was associated with poor survival rates for patients in different GC risk groups. BLACAT2 gene mutation was associated with poor disease-free survival outcome for patients with GC. The results suggest that PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC are potential biomarkers for the detection of GC at the molecular level and may be used as potential targets for GC therapy. The individual roles of these lncRNAs may be utilized for prognostic predictions.

Background: Early diagnosis improves the prognosis for non-small cell lung cancer (NSCLC); therefore, there is a pressing need for effective diagnostic methods for NSCLC. Increasing evidence indicates that serum exosomal micro RNAs (miRNAs) represent promising diagnostic and prognostic markers for multiple cancers. Here, we explored a panel of miRNAs for NSCLC diagnosis and functionally characterized miR-1269a in the pathogenesis of NSCLC. Methods: First, we analyzed high-throughput data from The Cancer Genome Atlas (TCGA) to identify differentially expressed miRNAs between NSCLC patients and healthy controls. We examined the expression profiles of the identified miRNAs using qRT-PCR. Results: We found that four micro-RNAs (hsa-miR-9-3p, hsa-miR-205-5p, hsa-miR-210-5p, and hsa-miR-1269a) were more abundant in serum exosomes from NSCLC patients. A logistic regression model validated the diagnostic efficacy of the four-microRNA panel, allowing us to distinguish NSCLC patients from healthy controls with AUCs of 0.915 and 0.878 for the training and validation sets, respectively. Functionally, NSCLC cell proliferation, migration, and invasion were affected by the aberrant expression of hsa-miR-1269a in culture. Reduced expression of miR-1269a resulted in reduced proliferation, migration, and invasion through targeting the forkhead box O1 gene (FOXO1). Conclusions: Taken together, our study identified a panel of four serum exosomal miRNAs as a potential noninvasive diagnostic biomarker for NSCLC. The interactions between FOXO1 and miR-1269a represent novel potential targets for NSCLC therapy.

Accumulating literatures have indicated that long non-coding RNAs (lncRNAs) are crucial molecules in tumor progression in various human cancers, including colorectal cancer (CRC). However, the clinical significance and regulatory mechanism of a vast majority of lncRNAs in CRC remain to be determined. The current study aimed to explore the function and molecular mechanism of lncRNA AC010789.1 in CRC progression. AC010789.1 found to be overexpressed in CRC tissues and cells. High expression of AC010789.1 was associated with lymph node metastasis and poor prognosis. Moreover, AC010789.1 silencing inhibited proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro as well as tumorigenesis and metastasis in vivo. Mechanistically, we demonstrated that repression of AC010789.1 promoted miR-432-3p expression, and miR-432-3p directly binds to ZEB1. We then proved the anti-tumor role of miR-432-3p in CRC, showing that the inhibitory effect of AC010789.1 knockdown on CRC cells was achieved by the upregulation of miR-432-3p but downregulation of ZEB1. We also established that silencing AC010789.1 suppressed the Wnt/β-catenin signaling pathway. However, this inhibitory effect was partially counteracted by inhibition of miR-432-3p. In summary, these results reveal that silencing AC010789.1 suppresses CRC progression via miR-432-3p-mediated ZEB1 downregulation and suppression of the Wnt/β-catenin signaling pathway, highlighting a potentially promising strategy for CRC treatment.