CircRNAs and cancer: Biomarkers and master regulators

Arnaiz, Esther; Solé, Carla; Manterola, Lorea; Iparraguirre, Leire; Otaegui, David; Lawrie, Charles H.

doi:10.1016/j.semcancer.2018.12.002

Cited by 332 publications

(256 citation statements)

References 158 publications

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“…Recent studies have highlighted promising potential of circRNAs as important modulators in human cancers 17,18. Our study conducted hsa_circRNA_002178 loss-of-function experiments and finally identified that hsa_cir-cRNA_002178 functioned as a miR-328-3p sponge and impaired miR-328-3p-targeted repression of COL1A1.The first observation was that high hsa_circRNA_002178 expression in breast cancer was associated with poor prognosis.Knockdown of hsa_circRNA_002178 suppressed aggressive malignant behaviours including cell proliferation and angiogenesis.…”

mentioning

confidence: 89%

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA‐328‐3p‐mediated inhibition of COL1A1

Liu

et al. 2020

J Cellular Molecular Medi

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Circular RNAs (circRNAs) are a group of non-coding RNAs implicated in the pathogenesis of cancer progression, which exert their functions via regulation of microRNAs (miRNAs) and genes. The present study uses gain-and loss-of-function approaches to evaluate the functions of hsa_circRNA_002178 in angiogenesis along with energy metabolism and underlying downstream signals. The expression pattern of hsa_cir-cRNA_002178 in clinical breast cancer tissues and its association with prognosis were characterized at first. Next, the energy metabolism and angiogenesis as well as cell viability were evaluated when the expression of hsa_circRNA_002178 in breast cancer cells was knocked down by siRNA. The interaction between hsa_circRNA_002178 and its downstream miR-328-3p was identified, followed by the analysis of their functions in regulation of breast cancer cellular behaviours. The target gene of miR-328-3p was predicted and verified, followed by identifying its role in the breast cancer progression. Higher expression of hsa_circRNA_002178 shared an association with worse prognosis in breast cancer. The inhibition of hsa_circRNA_002178 resulted in reductions in cell viability, energy metabolism and tube formation ability.Hsa_circRNA_002178 could competitively bind to miR-328-3p and down-regulated its expression. Restoration of miR-328-3p eliminated the tumour-promoting effects of hsa_circRNA_002178. COL1A1, as a target of miR-328-3p, could be up-regulated by overexpression of hsa_circRNA_002178. In vivo experiments further confirmed the inhibition of tumour growth and inflammation by silencing hsa_circRNA_002178 or up-regulating miR-328-3p. Taken together, hsa_circRNA_002178 is highlighted as a promising target for breast cancer due to the anti-tumour effects achieved by silencing hsa_circRNA_002178. K E Y W O R D S angiogenesis, breast cancer, circular RNA, COL1A1, energy metabolism, Hsa_ circRNA_002178, MicroRNA-328-3p Additional supporting information may be found online in the Supporting Information section. How to cite this article: Liu T, Ye P, Ye Y, Lu S, Han B. Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA-328-3p-mediated inhibition of COL1A1.

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confidence: 89%

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA‐328‐3p‐mediated inhibition of COL1A1

Liu

et al. 2020

J Cellular Molecular Medi

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“…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 . 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%

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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“…Studies have reported that the long non-coding RNA (lncRNA) RP11 promotes colorectal cancer cells dissemination by ZEB1 overexpression, whereas lncRNA HCCL5 could be activated by ZEB1 to promote hepatocellular carcinoma malignancy. 18,19 Among these, lncRNAs are a class of ncRNAs of more than 200 bp that have been demonstrated to be closely related to cancer progression, including tumorigenesis, 20 stemness, 21 apoptosis, 22 25 It has also been reported that LINC00511 promotes proliferation in pancreatic ductal adenocarcinoma, 26 ovarian cancer 27 and glioma. 16,17 Non-coding RNAs (ncRNAs) are transcribed genes that are not further translated into proteins and include lncRNAs, circular RNAs (circRNAs) and miRNAs, which perform vital roles in human cancers.…”

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confidence: 99%

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

Liu

et al. 2019

J Cellular Molecular Medi

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Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial‐mesenchymal transition. Long intergenic non‐coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up‐regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreover, ectopic LINC00511 enhanced GBM cells proliferation, EMT, migration and invasion, whereas LINC00511 knockdown had the opposite effects. Mechanistically, we confirmed that ZEB1 acted as a transcription factor for LINC00511 in GBM cells. Subsequently, we found that LINC00511 served as a competing endogenous RNA that sponged miR‐524‐5p to indirectly regulate YB1, whereas, up‐regulated YB1 promoted ZEB1 expression, which inversely facilitated LINC00511 expression. Finally, orthotopic xenograft models were performed to further demonstrate the LINC00511 on GBM tumorigenesis. This study demonstrates that a LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop provides potential therapeutic targets for GBM progression.

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CircRNAs and cancer: Biomarkers and master regulators

Cited by 332 publications

References 158 publications

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA‐328‐3p‐mediated inhibition of COL1A1

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA‐328‐3p‐mediated inhibition of COL1A1

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

LINC00511 contributes to glioblastoma tumorigenesis and epithelial‐mesenchymal transition via LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop

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