Circular RNAs in Cancer

Bach, Duc Hiep; Lee, Sang Kook; Sood, Anil K.

doi:10.1016/j.omtn.2019.02.005

Cited by 355 publications

(270 citation statements)

References 123 publications

(184 reference statements)

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“…Circular RNAs (circRNAs) are a newly discovered type of endogenous noncoding RNAs (ncRNAs) that are stably expressed in the eukaryotic transcriptome . Unlike other linear RNAs, circRNAs have a covalently closed, continuous loop structure . Because of this particular structure, circRNAs can be widely and stably expressed in cells and thus engaged in the regulation of cellular physiological activities and pathological processes .…”

Section: Introductionmentioning

confidence: 99%

“…6 Unlike other linear RNAs, circRNAs have a covalently closed, continuous loop structure. 7 Because of this particular structure, cir-cRNAs can be widely and stably expressed in cells and thus engaged in the regulation of cellular physiological activities and pathological processes. 8 Although circRNA was first discovered in 1976, it was only in recent years that its abnormal expression level was linked to the tumorigeneses and progression of diverse malignancies, including ESCC.…”

Section: Introductionmentioning

confidence: 99%

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Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Xu¹,

Xiaojing²,

Li³

et al. 2019

IUBMB Life

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Circular RNAs (circRNAs) are novel noncoding RNAs (ncRNAs) with covalently closed‐loop structures that play an essential regulatory role in diverse malignancies, including esophageal squamous cell cancer (ESCC). Circ_0000654 expression in ESCC and its mechanism of action remains unclear. Real‐time PCR (RT‐PCR) was employed to detect circ_0000654 and miR‐149‐5p expression in ESCC tissues. Circ_0000654 and miR‐149‐5p expression in ESCC cells was selectively regulated. Furthermore, interleukin 6 (IL‐6) and signal transducer and activator of transcription 3 (STAT3) expression in cells was detected by RT‐PCR and western blot analysis, while CCK8, BrdU, flow cytometry, and transwell assays were used to monitor cell proliferation, apoptosis, migration and invasion, respectively. The dual‐luciferase reporter assay and RIP assay were used to verify the targeting relationship between circ_0000654 and miR‐149‐5p, miR‐149‐5p and IL‐6. The function of circ_0000654 on ESCC cell proliferation and metastasis in vivo was examined using a subcutaneous xenograft model and a tail intravenous injection model in nude mice. Circ_0000654 was significantly upregulated in ESCC tissues and cell lines, and its high expression was remarkably associated with an increased T stage and local lymph node metastasis in ESCC patients. Circ_0000654 overexpression and knockdown experiments revealed that circ_0000654 regulated ESCC cell proliferation, migration, invasion, and apoptosis in vitro. Circ_0000654 was identified as a sponge of miR‐149‐5p and facilitated ESCC progression by indirectly activating the IL‐6/STAT3 signaling pathway. Additionally, knocking down circ_0000654 strikingly repressed ESCC growth and metastasis in vivo. In summary, circ_0000654 functions as an oncogenic circRNA in ESCC and accelerates ESCC progression via adsorbing miR‐149‐5p and activating the IL‐6/STAT3 signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Xu¹,

Xiaojing²,

Li³

et al. 2019

IUBMB Life

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“…The roles of circRNAs in cancer progression and carcinogenesis have attracted much attention. [24][25][26] While their function and expression in OVA remain largely elusive. Here, we F I G U R E 3 SOCS3 and miR-760 are downstream targets of hsa_circ_0007874.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of hsa_circ_0007874 suppresses the progression of ovarian cancer by regulating the miR‐760/SOCS3 pathway

Yu²,

Zhang

et al. 2020

Cancer Medicine

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Ovarian cancer (OVA) is a fatal and common malignancy in women worldwide. Circular RNAs (circRNAs) consist of a family of circular endogenous RNAs generated by selective splicing, and they are involved in many diseases. Previous studies reported that hsa_circ_0007874 is aberrantly expressed in cancer and functions in tumorigenesis. While the hsa_circ_0007874 role in OVA is unclear. Here, we detected the hsa_circ_0007874 expression in OVA cell lines using Rt‐qPCR. Hsa_circ_0007874 subcellular localization was confirmed by fluorescence in situ hybridization. The relationship between hsa_circ_0007874, microRNAs (miRNAs), and relative protein levels was assessed using the luciferase reporter assays. Results verified that hsa_circ_0007874 is downregulated in OVA cell lines. hsa_circ_0007874 overexpression decreased the OVA cell migration and proliferation in vitro and in vivo. Bioinformatics and luciferase reporter assays confirmed that miR‐760 and SOCS3 are the downstream targets of hsa_circ_0007874. Downregulation of SOCS3 or miR‐760 overexpression restored the migration and proliferation ability of SKOV3 or A2780 cells overexpressing hsa_circ_0007874. Downregulation of SOCS3 restored the proliferation and migration in miR‐760 knockdown SKOV3 and A2780 cells. In summary, the data suggest that hsa_circ_0007874 acts as a tumor suppressor by regulating the miR‐760/SOCS3 axis, highlighting its potential as an effective therapeutic target for OVA.

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“…CircRNA, a class of enclosed non-coding RNA molecules generated by RNA splicing, function as an miRNA sponge and regulate gene transcription and alternative splicing [18,19,8,13,4,5]. Recent studies have confirmed that circRNA is involved in the regulation of gene expression by various means, thereby indirectly participating in the occurrence and development of various solid cancers [13,11,10,6,17,9,16,14].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, it has been confirmed that cirRNA can regulate the expression of its target gene via a micro RNA (miRNA) sponge, and that it can adjust pre-mRNA splicing to influence protein production [6,7]. In addition, circRNA can directly bind to proteins, or establish an indirect RNA-mediated association with proteins to influence their functions [8]. Studies have reported that circRNA is closely correlated with the occurrence and development of various malignant tumors, including liver cancer [9,10], lung cancer [11,12], cervical cancer [13] gastric cancer [14,15], colorectal cancer [16,17], etc.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA hsa_circ_0068033 inhibits proliferation and invasion of breast cancer cells through sponging miR-659

Yuan

Lei

Liu

2019

Preprint

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Recently, dysregulated circular RNAs (circRNAs) have been associated with the progression of numerous malignant tumors. However, the mechanism through which circRNAs participate in breast cancer (BC) remains unclear. This study was designed to illustrate the role of hsa_circ_0068033 in BC. A series of functional experiments were conducted to assess the function of hsa_circ_0068033 in the development of BC and the underlying mechanisms. The results suggested that the expression of hsa_circ_0068033 was downregulated in BC tissues, and markedly correlated with tumor size (P=0.021) and the Tumor, Node, and Metastasis stage (P=0.023). Receiver operating characteristic analysis showed that hsa_circ_0068033 testing yielded an area under the curve value of 0.8480 in discriminating BC from non-tumor controls.Functionally, overexpression of hsa_circ_0068033 could inhibit the growth, clone formation, invasion, and migration of MCF-7 and MDA-MB-231 cells, while activating the intrinsic apoptotic pathway to induce apoptosis. The xenograft experiment revealed that exogenous hsa_circ_0068033 is able to reduce the tumorigenic ability of MDA-MB-231 cells in nude mice. Rescue assays further proved that hsa_circ_0068033 exerts biological functions by sponging miR-659. This study revealed for the first time that hsa_circ_0068033 acts as a tumor suppressor gene in BC, and the hsa_circ_0068033/miR-659 axis participates in the progression of BC.

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Circular RNAs in Cancer

Cited by 355 publications

References 123 publications

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Circular RNA hsa_circ_0000654 promotes esophageal squamous cell carcinoma progression by regulating the miR‐149‐5p/IL‐6/STAT3 pathway

Upregulation of hsa_circ_0007874 suppresses the progression of ovarian cancer by regulating the miR‐760/SOCS3 pathway

Circular RNA hsa_circ_0068033 inhibits proliferation and invasion of breast cancer cells through sponging miR-659

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