A circular RNA promotes tumorigenesis by inducing c-myc nuclear translocation

Yang, Qi; Du, William W.; Wu, Nan; Yang, Weining; Awan, Faryal Mehwish; Fang, Ling; Ma, Jian; Li, Xiangmin; Zeng, Yan; Yang, Zhen-Guo; Dong, Jun; Khorshidi, Azam; Yang, Burton B.

doi:10.1038/cdd.2017.86

Cited by 261 publications

(209 citation statements)

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“…circ‐Amotl1 is highly expressed both in patient tumor samples and in breast cancer cell lines, where it acts as an oncogene promoting cancer growth (Yang et al ., ). circ‐Amotl1 interacts with c‐myc increasing the retention of nuclear c‐myc, promoting c‐myc stability, and upregulating c‐myc targets.…”

Section: Known Mechanisms Of Action Of Circrnasmentioning

confidence: 97%

“…circ‐Amotl1 interacts with c‐myc increasing the retention of nuclear c‐myc, promoting c‐myc stability, and upregulating c‐myc targets. Indeed, the complex circ‐Amotl1/c‐myc increases the affinity of c‐myc binding to the promoters of the genes HIF‐1g , Cdc25a , ELK‐1 , and JUN (Yang et al ., ). Once again, this proves how the function of circular RNAs and the function of the respective host genes are ruled by different mechanisms even if both molecules promote cancer progression.…”

Section: Known Mechanisms Of Action Of Circrnasmentioning

confidence: 97%

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The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

Verduci¹,

Strano²,

et al. 2019

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Circular RNA s (circ RNA s) comprise an emerging new class of endogenous RNA s expressed abundantly by the eukaryotic transcriptome. They are characterized by a covalently closed loop structure, resulting in RNA molecules that are more stable than linear RNA s. A growing number of studies indicate that circ RNA s play critical roles in human diseases and show great potential as biomarkers and therapeutic targets. The molecular events determined by circ RNA activity, the circ RNA code, involve other types of noncoding RNA molecules, primarily micro RNA s, long noncoding RNA s, and RNA ‐binding proteins. Herein, we mainly focus on the circ RNA –micro RNA code, showing how this relationship impacts the regulation of gene expression in cancer. The emerging roles for circ RNA s in oncogenic pathways highlight new perspectives for the detailed molecular dissection of cancer pathogenesis and, at the same time, offer new opportunities to design innovative therapeutic strategies. Here, we review recent research advancements in understanding the biogenesis, molecular functions, and significance of circ RNA s in cancer diagnosis and treatment.

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Section: Known Mechanisms Of Action Of Circrnasmentioning

confidence: 97%

Section: Known Mechanisms Of Action Of Circrnasmentioning

confidence: 97%

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

Verduci¹,

Strano²,

et al. 2019

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“…In contrast to the vast majority of exon‐derived circRNAs that are located in the cytoplasm, circ‐Amotl1 (hsa_circ_0004214) tends to interact with and stabilize oncogene C‐MYC in the nucleus. Hsa_circ_0004214 enhances C‐MYC binding to the promoters of hypoxia‐inducing factor (HIF)‐1α, cell division cycle 25 homolog A (Cdc25a), ETS domain‐containing protein (ELK1), and JUN, thus promoting cell proliferation, invasion and colony formation …”

Section: Functions Of Circrnasmentioning

confidence: 99%

Circular RNAs in hepatocellular carcinoma: Functions and implications

Jiang

et al. 2018

Cancer Medicine

107

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At present, as hotspot members of the noncoding RNA network, circular RNAs (circRNAs) with distinct properties and diverse pathophysiological functions are being increasingly delineated. CircRNAs play roles at the epigenetic, transcriptional and posttranscriptional regulatory levels. Major studies have focused on their functions as efficient microRNA sponges. The validated number of endogenous circRNAs involved in hepatocellular carcinoma (HCC) continues to increase. Altered circRNA expression is associated with HCC occurrence, invasion, and metastasis. Moreover, the aberrant expression of circRNAs is also significantly related to HCC tumor stage, size, differentiation and metastasis. Because they are exceptionally stable, highly conserved and have tissue‐specific expression patterns, some circRNAs, including hsa_circ_0004018, hsa_circ_0003570, and hsa_circ_0005075, may be potential markers for the diagnosis of HCC. We herein summarize the current knowledge of HCC‐associated circRNAs and present their implications for carcinogenesis and their potential value as diagnostic and prognostic biomarkers. Finally, we discuss the future directions of studies on HCC‐associated circRNAs.

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“…Apart from functioning as miRNA sponge, limited studies illustrated the importance of circRNA-protein interaction. circ-Amotl1 interacted with c-myc and promoted c-myc translocation to nucleus in breast cancer 33 . Circ-CTNNB1 interacted with DDX3 to transactivate YY1 and YY1 downstream targets in gastric cancer 34 .…”

Section: Discussionmentioning

confidence: 98%

CircFOXK2 Promotes Tumor Growth and Metastasis of Pancreatic Ductal Adenocarcinoma via Complexing with RNA Binding Proteins and Sponging MiR-942

Wong

Lou

et al. 2019

Preprint

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Objective: Circular RNA (circRNA) is a novel class of non-coding RNAs that regulate gene expression. However, the role of circRNAs in pancreatic ductal adenocarcinoma (PDAC) is largely unknown. Design:We performed circRNA sequencing of non-tumor HPDE and PDAC cells. We investigated the functions of circFOXK2 in PDAC by gain-of-function and loss-of-function assays. Bioinformatics analysis, luciferase assay and microRNA pulldown assays were performed to identify circFOXK2 interacting-miRNAs. To further investigate the mechanism, we performed circRNA-pulldown and mass spectrometry to identify circFOXK2-interacting proteins in PDAC. Results:We identified 169 differentially expressed circRNAs in PDAC cells. We validated that one of the circRNAs circFOXK2 was significantly up-regulated in PDAC cells and in 63 % of primary tumor (53 out of 84). Gain-of-function and loss-of-function assays demonstrated that circFOXK2 promoted PDAC cell growth, migration and invasion. CircFOXK2 was also involved in cell cycle progression and apoptosis. circFOXK2 functioned as sponge for miR-942, and in turn promoted the expression of miR-942 targets ANK1, GDNF and PAX6. Furthermore, circFOXK2 interacted with 94 proteins, which were involved in cell adhesion and mRNA splicing. Among these circFOXK2-interacting proteins, YBX1 and hnRNPK were validated by RNA immunoprecipitation. Importantly, circFOKX2 interacted with YBX1 and hnRNPK targets NUF2 and PDXK in PDAC cells. Knockdown of circFOXK2 reduced the binding of YBX1 and hnRNPK to NUF2 and PDXK, and in turn decreased their expressions in PDAC cells. Conclusion:We identified that circFOXK2 promoted PDAC cells growth and metastasis. Also, circFOXK2 complexed with YBX1 and hnRNPK to promote the expressions of oncogenic proteins.• circFOXK2 upregulation in PDAC may function as a novel biomarker for diagnosis.• circFOXK2 may be a novel therapeutic target in treating PDAC.

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A circular RNA promotes tumorigenesis by inducing c-myc nuclear translocation

Cited by 261 publications

References 50 publications

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

The circRNA–microRNA code: emerging implications for cancer diagnosis and treatment

Circular RNAs in hepatocellular carcinoma: Functions and implications

CircFOXK2 Promotes Tumor Growth and Metastasis of Pancreatic Ductal Adenocarcinoma via Complexing with RNA Binding Proteins and Sponging MiR-942

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