Circular RNAs (circRNAs) are a class of noncoding RNAs that are differentially expressed in tissues with a great potential in regulating the tumorigenesis and metastasis. The COX proportional hazard model predicts that among these, the relative expression of circRNA_104916 and lymphatic metastatic status independently predict the prognosis of patients with cancer. In the present study, we show that circRNA_104916 is downregulated in colorectal cancers as compared to the adjacent normal tissues. The expression of circRNA_104916 is negatively correlated with the tumor size, T stage and lymphatic metastasis. Patients with higher relative circRNA_104916 expression have a better post-operative disease-free survival as compared with those with lower relative expression. Forced expression of circRNA_104916 induces cell apoptosis and G2/M phase arrest by activating apoptosis pathway and cyclin proteins, thereby inhibiting proliferation of colon cancer cell lines, including LoVo and Caco-2. Additionally, overexpression of circRNA_104916 significantly suppresses migration and invasion of tumor cells by inhibiting the epithelial-mesenchymal transition. In conclusion, this study reveals that circRNA_104916 is a potential biomarker and therapeutic target for colorectal cancers.

Recently, Up-frameshift protein 1 (UPF1) is reported to be downregulated in various cancers and its low expression is closely correlated with poor prognosis. UPF1 is well known as a master regulator of nonsense-mediated mRNA decay (NMD), which serves as a highly conserved mRNA surveillance process protecting cells from aberrant toxic transcripts. Due to dysfunction of UPF1, NMD fails to proceed, which contributes to tumor initiation and progression. This review shows a brief summary of the aberrant expression, functional roles and molecular mechanisms of UPF1 during tumorigenesis. Increasing evidence has indicated that UPF1 could serve as a potential biomarker for cancer diagnosis and treatment for future clinical applications in cancer.

The present study aimed to investigate the biological function and relative mechanisms of circRNA_100876 in gastric cancer (GC). To this end, quantitative real-time polymerase chain reaction (RT-qPCR) was performed to examine the expression of circRNA_100876 and miR-665 in GC tissues and cells, and circRNA_100876 expression was depleted by the transfection of circ_100876-targeting siRNAs. CCK-8, flow cytometry, and Transwell assays were applied to examine GC cell cycle distribution, proliferation, apoptosis, migration, and invasion abilities. Proteins related to apoptosis and epithelial-mesenchymal transition (EMT) were detected by western blotting. Luciferase reporter assays were conducted to verify the direct target site between circRNA_100876 and miR-665. Our study confirmed that circRNA_100876 was highly expressed in GC lesions compared with the adjacent normal tissues (P < 0.001). High circRNA_100876 expression was negatively associated with survival outcome (P = 0.000). Furthermore, the down-regulation of circRNA_100876 could inhibit GC cell proliferation, invasion, and migration by suppressing the EMT pathway. Further study suggested that circRNA_100876 could act as a competing endogenous RNA by sequestering miR-665, and luciferase activity assay indicated that circRNA_100876 could bind directly with miR-665. Moreover, we found that Yes-associated protein 1 (YAP1) was the downstream target gene of miR-665, miR-665 knockdown could up-regulate YAP1 expression in MKN45 cells, and YAP1 knockdown could inhibit MKN45 cell proliferation, migration and invasion. Therefore, we demonstrated that circRNA_100876 over-expression in GC could promote GC tumor growth, migration and invasion and exert its effects through miR-665/YAP1 signaling.

Background: Recently, accumulating evidence confirmed that up-frameshift protein 1 (UPF1) was aberrantly expressed in various cancers. However, the molecular mechanism mediated by UPF1 underlying colorectal carcinogenesis remains unclear. Method: Immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction analysis were used to determine the expression level of UPF1 in colorectal cancer (CRC) tissues. CCK-8, EdU, transwell assay, and flow cytometry were performed to investigate the biological significance of UPF1. Epithelial–mesenchymal transition (EMT) and apoptosis associated markers were detected by western blotting. Results: We found that UPF1 expression was upregulated in CRC tissues and cell lines. Clinical analysis revealed that high UPF1 expression was positively correlated with advanced stage, lymph node metastasis and shorter survival. Knockdown of UPF1 suppressed cell proliferation and cell cycle progression. Functionally, UPF1 promotes tumor metastasis by inducing epithelial to mesenchymal transition. Further investigations revealed that knockdown of UPF1 promoted apoptosis through triggering DNA damage. Conclusions: Taken together, this research revealed that UPF1 plays an oncogenic role in CRC via regulating EMT and apoptosis and may be a potential therapeutic target for CRC.

Purpose: This study aimed to explore the function and clinical significance of AVL9 in colorectal cancer (CRC). Materials and Methods: The GEO, TCGA, and GEPIA databases were searched to evaluate the expression level of AVL9, while the SurvExpress online tool was used to explore its related clinical survival prognosis. The cBioPortal and LinkedOmics databases were used to identify AVL9 expression-related genes. Protein–protein interaction (PPI) networks were analyzed using Cytoscape 3.7.1 and DAVID6.8, which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment. The immunohistochemistry of AVL9 in CRC was detected using an online tool protein atlas. RNA isolation and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) assays were used to detect AVL9 expression in tissue and plasma samples. Results: Our study confirmed that AVL9 was highly expressed in CRC lesions versus the adjacent normal tissues (P < 0.001). High AVL9 expression was negatively associated with survival outcomes (P < 0.05). GO analysis showed that AVL9 expression-related genes were enriched in single organismal cell–cell adhesion, post-transcriptional regulation of gene expression, and negative regulation of the vascular endothelial growth factor receptor signaling pathway (P < 0.05). On a KEGG pathway analysis, these genes were mainly involved in progesterone-mediated oocyte maturation, axon guidance, the insulin signaling pathway, and the ubiquitin-mediated proteolysis signaling pathways (P < 0.05). In the PPI analysis, the KBTBD2, KIAA1147, EPDR1, and RNF216 genes interacted with AVL9, and GEPIA predicted that their expression levels were all positively correlated with AVL9. Furthermore, a clinicopathological parameter analysis found that high AVL9 expression was positively correlated with differentiation and TNM stage. RT-qPCR analysis further showed that plasma AVL9 expression was upregulated in CRC patients versus healthy controls. Conclusion: AVL9 could serve as a potential biomarker and therapeutic target for CRC.