Abstract:microRNAs (miRNAs) regulate gene expression at post-transcriptional level by repressing target RNA molecules. Competition to bind miRNAs tends in turn to correlate their targets, establishing effective RNA-RNA interactions that can influence expression levels, buffer fluctuations and promote signal propagation. Such a potential has been characterized mathematically for small motifs both at steady state and away from stationarity. Experimental evidence, on the other hand, suggests that competing endogenous RNA … Show more
“…The ceRNA hypothesis has proposed that RNA transcripts may construct a complex post-transcriptional regulatory network, in which mRNAs, lncRNAs, and circRNAs share the same miRNA response elements, competing for binding miRNAs, and then regulating expression of each other. [29][30][31][32] For instance, circTP63 contains miR-873-3p-binding sites and regulates FOXM1 expression via miR-873-3p in lung squamous cell carcinoma. 19 In CRC, miR-597-5p was verified as the binding target of circ101555 and promotes tumor growth by regulating CSNK1G1.…”
Background: Emerging evidence suggests that circular RNAs (circRNAs) are vital regulators in a range of cancers. "miRNA sponge" is the most reported role played by circRNAs in many tumors. The insulin-like growth factor (IGF) 1 pathway plays a key role in the development and progression of many cancers, including colorectal cancer (CRC). The aim of the study is to establish the potential clinical value and driving molecular mechanisms of circRNAs in CRC. Materials and Methods: Real-time quantitative RT-PCR (qRT-PCR) was performed to measure the circRUNX1 expression in 52 tissue samples from CRC patients. We verified the tumor promotor role of circRUNX1 in cell-based in vitro and in vivo assays. Human growth factor array was used to identify circRUNX1-regulated signaling pathways. We then used a double luciferase reporter assay and RNA fluorescence in situ hybridization to identify the downstream miR-145-5p of circRUNX1. Furthermore, we performed Western blotting and biological function assays to demonstrate if the circRUNX1/miR-145-5p/IGF1 axis is responsible for the proliferation of CRC cells and promotes CRC development. Results: By performing qRT-PCR from CRC tissues and paired adjacent normal mucosa tissues, we identified that circRUNX1 expression was significantly upregulated in CRC tissues and positively related with lymph node metastasis, distant metastasis and advanced tumor-node-metastasis tumor stage in patients. Functionally, circRUNX1 knockdown inhibited cell proliferation and migration and promoted apoptosis, whereas its overexpression exerted opposite effects. In vivo, circRUNX1 promoted tumor growth and metastasis. Mechanically, circRUNX1 shared miRNA response elements with IGF1. circRUNX1 competitively bound to miR-145-5p and prevented miR-145-5p from decreasing the expression of IGF1, which facilitated tumor growth. Conclusion: Our studies verified that circRUNX1 functions as a tumor promotor in CRC cells by targeting the miR-145-5p/IGF1 signaling pathway and may have potential use as a prognostic indicator and therapeutic target in CRC patients.
“…The ceRNA hypothesis has proposed that RNA transcripts may construct a complex post-transcriptional regulatory network, in which mRNAs, lncRNAs, and circRNAs share the same miRNA response elements, competing for binding miRNAs, and then regulating expression of each other. [29][30][31][32] For instance, circTP63 contains miR-873-3p-binding sites and regulates FOXM1 expression via miR-873-3p in lung squamous cell carcinoma. 19 In CRC, miR-597-5p was verified as the binding target of circ101555 and promotes tumor growth by regulating CSNK1G1.…”
Background: Emerging evidence suggests that circular RNAs (circRNAs) are vital regulators in a range of cancers. "miRNA sponge" is the most reported role played by circRNAs in many tumors. The insulin-like growth factor (IGF) 1 pathway plays a key role in the development and progression of many cancers, including colorectal cancer (CRC). The aim of the study is to establish the potential clinical value and driving molecular mechanisms of circRNAs in CRC. Materials and Methods: Real-time quantitative RT-PCR (qRT-PCR) was performed to measure the circRUNX1 expression in 52 tissue samples from CRC patients. We verified the tumor promotor role of circRUNX1 in cell-based in vitro and in vivo assays. Human growth factor array was used to identify circRUNX1-regulated signaling pathways. We then used a double luciferase reporter assay and RNA fluorescence in situ hybridization to identify the downstream miR-145-5p of circRUNX1. Furthermore, we performed Western blotting and biological function assays to demonstrate if the circRUNX1/miR-145-5p/IGF1 axis is responsible for the proliferation of CRC cells and promotes CRC development. Results: By performing qRT-PCR from CRC tissues and paired adjacent normal mucosa tissues, we identified that circRUNX1 expression was significantly upregulated in CRC tissues and positively related with lymph node metastasis, distant metastasis and advanced tumor-node-metastasis tumor stage in patients. Functionally, circRUNX1 knockdown inhibited cell proliferation and migration and promoted apoptosis, whereas its overexpression exerted opposite effects. In vivo, circRUNX1 promoted tumor growth and metastasis. Mechanically, circRUNX1 shared miRNA response elements with IGF1. circRUNX1 competitively bound to miR-145-5p and prevented miR-145-5p from decreasing the expression of IGF1, which facilitated tumor growth. Conclusion: Our studies verified that circRUNX1 functions as a tumor promotor in CRC cells by targeting the miR-145-5p/IGF1 signaling pathway and may have potential use as a prognostic indicator and therapeutic target in CRC patients.
“…Plentiful researches have proved that lncRNAs act as a competing endogenous RNA (ceRNA) to get involved in cancer. In brief, lncRNAs can serve as sponges for miRNAs to modulate mRNAs [12,13]. In other words, lncRNAs release mRNAs by binding with miRNAs.…”
Background
Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet.
Methods
RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified.
Results
LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression.
Conclusions
LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.
“…Increasing evidence has showcased that lncRNAs could affect protein‐coding gene expression post‐transcriptionally via sponging certain miRNAs, and such regulatory mechanism is referred to competing endogenous RNA (ceRNA) network 14 . In present study, miR‐224‐5p was predicted as the miRNA interacting with LINC00665.…”
Melanoma is an aggressive malignant skin tumor endangering the health of patients. Long non‐coding RNAs (lncRNAs) and microRNAs (miRNAs) have been increasingly reported to be implicated in the carcinogenesis of melanoma. Long intergenic non‐coding RNA 00665 (LINC00665) has been found to exert important regulatory roles in some cancers, yet its function in melanoma remains to be investigated. QRT‐PCR analysis was conducted to evaluate the relative expression of RNAs. Functional experiments in vitro including colony formation, EdU, wound‐healing and transwell assays, as well as in vivo xenograft assays, were utilized to study the role of LINC00665 in melanoma. Mechanical experiments were implemented to probe into the molecular linkage of LINC00665, miR‐224‐5p and VMA21. LINC00665 was abnormally highly expressed in melanoma cells. Silencing LINC00665 could inhibit the proliferation and migration of melanoma cells. LINC00665 sponged miR‐224‐5p to upregulate VMA21. VMA21 knockdown exerted similarly interfering effects on above biological processes in melanoma cells. However, VMA21 overexpression abolished the in vitro and in vivo outcomes of LINC00665 silencing. LINC00665 promotes proliferative and migrating abilities of melanoma cells via targeting miR‐224‐5p/VMA21 axis.
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