Splicing factor derived circular RNA circUHRF1 accelerates oral squamous cell carcinoma tumorigenesis via feedback loop

Zhao, Wei; Cui, Yameng; Liu, Lina; Qi, Xiaoqian; Li, Jingwen; Ma, Shiqing; Hu, Xin; Zhang, Zheng; Wang, Yue; Li, Hongfa; Wang, Zuomin; Liu, Zihao; Wu, Jie

doi:10.1038/s41418-019-0423-5

Cited by 159 publications

(131 citation statements)

References 41 publications

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“…CircIRAK3 is increased in metastatic BC cells and predictive recurrence, constructing the circIRAK3/miR-3607/FOXC1/IRAK3 positive-feedback loop 25 . The generated circRNAs are distributed both in cytoplasm and nucleus, and the subcellular distribution determines the functions of circRNAs 26 . The cytoplasmic circRNA could target the miRNA, acting as miRNA sponge, to indirectly regulate the functional proteins.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

et al. 2020

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Compelling evidence has demonstrated the potential functions of circular RNAs (circRNAs) in breast cancer (BC) tumorigenesis. Nevertheless, the underlying mechanism by which circRNAs regulate BC progression is still unclear. The purpose of present research was to investigate the novel circRNA circRNF20 (hsa_circ_0087784) and its role in BC. CircRNA microarray sequencing revealed that circRNF20 was one of the upregulated transcripts in BC samples. Increased circRNF20 level predicted the poor clinical outcome in BC specimens. Functionally, circRNF20 promoted the proliferation and Warburg effect (aerobic glycolysis) of BC cells. Mechanistically, circRNF20 harbor miR-487a, acting as miRNA sponge, and then miR-487a targeted the 3'-UTR of hypoxia-inducible factor-1α (HIF-1α). Moreover, HIF-1α could bind with the promoter of hexokinase II (HK2) and promoted its transcription. In conclusion, this finding illustrates the vital roles of circRNF20 via the circRNF20/ miR-487a/HIF-1α/HK2 axis in breast cancer progress and Warburg effect, providing an interesting insight for the BC tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

et al. 2020

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“…The in silico analyses were complemented by functional characterization of a novel, pro-tumorigenic circRNA, named circFLNB, thus substantiating the tumorigenic role of the OSCC-associated circRNAome. Lending further support to this notion, a recent study has also discovered an OSCC-associated, splicing factor-derived circRNA, named circUHRF1, and demonstrated its involvement in tumorigenesis [30]. Interestingly, a circRNA (circFLNA) derived from another filamin family gene, filamin A, was reported to impact the migration of the laryngeal squamous cell carcinoma, which is related histologically and anatomically to oral cancer [31].…”

Section: Discussionmentioning

confidence: 86%

circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response

Chen

Chang

Kan

et al. 2020

Cells

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Deep sequencing technologies have revealed the once uncharted non-coding transcriptome of circular RNAs (circRNAs). Despite the lack of protein-coding potential, these unorthodox yet highly stable RNA species are known to act as critical gene regulatory hubs, particularly in malignancies. However, their mechanistic implications in tumor outcome and translational potential have not been fully resolved. Using RNA-seq data, we profiled the circRNAomes of tumor specimens derived from oral squamous cell carcinoma (OSCC), which is a prevalently diagnosed cancer with a persistently low survival rate. We further catalogued dysregulated circRNAs in connection with tumorigenic progression. Using comprehensive bioinformatics analyses focused on co-expression maps and miRNA-interaction networks, we delineated the regulatory networks that are centered on circRNAs. Interestingly, we identified a tumor-associated, pro-tumorigenic circRNA, named circFLNB, that was implicated in maintaining several tumor-associated phenotypes in vitro and in vivo. Correspondingly, transcriptome profiling of circFLNB-knockdown cells showed alterations in tumor-related genes. Integrated in silico analyses further deciphered the circFLNB-targeted gene network. Together, our current study demarcates the OSCC-associated circRNAome, and unveils a novel circRNA circuit with functional implication in OSCC progression. These systems-based findings broaden mechanistic understanding of oral malignancies and raise new prospects for translational medicine.

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“…By gain-and loss-functional experiments, we further found that overexpression of circ_0000199 was able to promote cell proliferation and inhibit apoptosis, while knockdown of circ_0000199 exhibited opposite effects. Previous studies have shown that circRNAs, as a new type of competitive endogenous RNA (ceRNA), act as miRNA sponge by which interact with miRNA to cause dysregulated expression of miRNA target genes, thereby participating in OSCC process 25,26 . In this study, bioinformatics software predicted that circ_0000199 could interact with miR-145-5p and miR-29b-3p, which were downregulated in OSCC cells.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

Luo

Liu

Guo

et al. 2020

Sci Rep

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Studies have found that circRnA in exosomes is associated with oral squamous cell carcinoma (oScc) progression. In this study, we examined the expression of circ_0000199 in circulating exosomes from patients with oScc and its role in the evaluation of relapse and prognosis. Real-time quantitative reverse transcription-polymerase chain reaction was performed to assess circ_0000199 expression in circulating exosomes from 108 patients with OSCC and 50 healthy people. Gain-and loss-functional experiments were performed to assess the role of circ_0000199 on cell proliferation and apoptosis in OSCC cells. Our results showed that the high level of circ_0000199 in circulating exosomes was significantly associated with betel quid chewing, tumor size, lymphatic metastasis, and TNM stage in patients with OSCC. In addition, the patients with high exosomal circ_0000199 had higher tumor recurrence rate and higher mortality rate than the patients with low exosomal circ_0000199. Overexpression of circ_0000199 promoted, while knockdown of circ_0000199 inhibited OSCC cell growth. Bioinformatics analysis predicted that circ_0000199 interacted with miR-145-5p and miR-29b-3p simultaneously, which were involved in multiple tumor-related signaling pathways. in conclusion, upregulation of circ_0000199 in circulating exosomes from patients with OSCC is positively associated with poor survival outcome. Circulating exosomal circ_0000199 can be used as a biomarker and potential therapeutic target for oScc. Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the world, accounting for 3% of malignant tumors 1. Although the treatment of OSCC has made breakthroughs in the past decades, the 5-year mortality rate is still less than 50% 2. Early diagnosis and early treatment are the keys to improve the survival rate of patients with OSCC. Exosomes have phospholipid bilayer membrane with the markers TSG101 and CD63. The size of exosomes ranges from 30 to 100 nm. These vesicles exist in almost all body fluids of the human body, including blood, serum, saliva, cerebrospinal fluid, and urine 3. Exosomes contain various substances, such as proteins, DNA, microRNA (miRNA), circular RNA (circRNA). These molecules can be transported to regulate the signaling pathways of the recipient cells 4. CircRNAs are covalently formed from the ends of a single RNA molecule, without 5′ and 3′ ribonucleotide end, and circRNAs are expressed abundantly, conserved and stably in cells with temporal and spatial specificity 5. CircRNAs can bind to miRNAs to inhibit their functions. Therefore, circRNA is also called miRNA sponge. With the continuous understanding of circRNA, researchers have found that circRNAs are widely involved in the occurrence and development of physiology and disease as well as tumors 6. As a new type of regulatory endogenous RNA, circRNAs are expected to become a tumor diagnostic marker and therapeutic target due to its characteristics such as stability, conservation, and tissue-specific expression 7. For example, circRNA_...

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Splicing factor derived circular RNA circUHRF1 accelerates oral squamous cell carcinoma tumorigenesis via feedback loop

Cited by 159 publications

References 41 publications

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response

Upregulation of circ_0000199 in circulating exosomes is associated with survival outcome in OSCC

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