Circular RNA ciRS-7 Maintains Metastatic Phenotypes as a ceRNA of miR-1299 to Target MMPs

Sang, Meixiang; Meng, Lingjiao; Liu, Sihua; Ding, Pingan; Chang, Sheng; Ju, Yingchao; Liu, Fei; Gu, Lina; Lian, Yishui; Geng, Cuizhi

doi:10.1158/1541-7786.mcr-18-0284

Cited by 79 publications

(65 citation statements)

References 34 publications

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“…Our finding was similar to previous studies, circRNA ciRS-7 could act as the ceRNA of miR-1299 to promote migration and invasion of triple-negative breast cancer cells. 30 Taken together, circ_0006528 might regulate the resistance of breast cancer cells to PTX by binding to miR-1299.…”

Section: Discussionmentioning

confidence: 99%

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

Liu

Zhang

et al. 2020

OTT

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Background: Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTXresistant breast cancer progression. Methods: The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 (CDK8) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or CDK8 was predicted by online database confirmed by dualluciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_0006528 on tumor growth in vivo. Results: Circ_0006528 was significantly up-regulated and miR-1299 was down-regulated in PTX-resistant breast cancer tissues and cells compared with control groups. CDK8 protein expression was dramatically upregulated in PTX-resistant breast cancer tissues and cells as compared to control groups. Loss-of-function experiments revealed that circ_0006528 knockdown decreased IC50 value of PTX and restrained proliferation, migration, invasion and autophagy, whereas induced apoptosis of PTX-resistant breast cancer cells in vitro. The inhibitory effects of sh-circ_0006528 on the progression of PTX-resistant breast cancer cells were reversed by decreasing miR-1299 or increasing CDK8 expression. Furthermore, circ_0006528 could modulate CDK8 expression by sponging miR-1299. Circ_0006528 silencing impeded the growth of PTX-resistant tumors by regulating miR-1299/CDK8 axis in vivo. Conclusion: Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.

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Section: Discussionmentioning

confidence: 99%

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

Liu

Zhang

et al. 2020

OTT

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“…Previous studies have demonstrated that circular RNAs play a central regulatory role in the pathogenesis of a variety of cancer types (7,8). Studies have also verified that circular RNAs, as competitive endogenous RNAs, bind to miRNAs and regulate the expression of downstream target genes (9)(10)(11). For example, circular RNA circNASP has been shown to regulate OS malignant behavior via the miR-1253/FOXF1 axis (12).…”

Section: Introductionmentioning

confidence: 98%

CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

Xie

Chen

et al. 2020

Int J Mol Med

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Osteosarcoma (OS) is a primary malignant tumor with a complex etiology. Therefore, research into the pathogenesis of osteosarcoma is considered a priority. circular RNAs play important roles in cell metabolism and in the immune response and are closely associated with cancer treatment. However, research into the association of circular RNAs with osteosarcoma is limited. In the present study, circSAMd4A was validated by RT-qPcR and agarose gel electrophoresis. circSAMd4A and miR-342-3p expression was detected by RT-qPcR. The relative protein expression levels were measured by western blot analysis. MTT assay and flow cytometry were used to detect cell cytotoxicity and apoptosis, respectively. Transwell assay was applied to assess cell migration and invasion. dual-luciferase reporter assay was used to determine the association among circSAMd4A, Frizzled-7 (FZd7) and miR-342-3p. In vivo, subcutaneous tumor formation assay was performed in an experiment with nude mice. The results revealed that the expression levels of circSAMd4A and FZd7 were upregulated, while those of miR-342-3p were downregulated in OS tissues and cells. The inhibition of circSAMd4A suppressed cell progression and epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in OS. The reduction of miR-342-3p reversed the effects of circSAMd4A downregulation on cell cytotoxicity, migration, invasion, apoptosis and EMT in OS, while FZd7 overexpression blocked the effect of miR-342-3p upregulation on OS progression. The suppressive effect of sh-circSAMd4A on tumor growth was thus verified in OS. Overall, the present study demonstrated that circSAMd4A affected cell cytotox-icity, invasion, apoptosis, migration and EMT by regulating the miR-342-3p/FdZ7 axis in OS, thereby providing a novel regulatory mechanism and a potential therapeutic target for OS.

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“…CircRNAs can regulate target gene expression by interacting with corresponding microRNAs (miRNAs) (Zhang et al, 2015). CircRNAs can function as miRNA "sponges" and regulate gene transcription (Hansen et al, 2013;Sang et al, 2018). For example, circRNA-ITCH increases ITCH gene expression by acting as an miRNA sponge by interacting with miR-7, miR-17, and miR-214.…”

Section: Introductionmentioning

confidence: 99%

Hsa_Circ_0007843 Acts as a mIR-518c-5p Sponge to Regulate the Migration and Invasion of Colon Cancer SW480 Cells

Han

Luo

et al. 2020

Front. Genet.

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Circular RNA (circRNA), a type of RNA that is widely expressed in mammalian cells, is considered to be essential in tumorigenesis. CircRNA can regulate target gene expression by interacting with the corresponding microRNA (miRNA). Our preliminary results showed that the expression levels of 1,817 circRNAs were significantly different in colon cancer tissue compared with paracancerous tissue, of which 1,236 were upregulated and 581 were downregulated. By using RT-PCR, we confirmed that the expression of hsa_circ_0007843, hsa_circ_0010575, hsa_circ_0007331, and hsa_circ_0001615 was significantly higher in colon cancer tissue than in normal colonic tissue; however, the expression levels of hsa_circ_0014879 and hsa_circRNA_401801 were not significantly different between normal and neoplastic colonic tissue. Among the circRNAs that were confirmed to be upregulated in colon cancer tissue, hsa_circ_0007843 was also found to be highly expressed in colon cancer SW480 cells. Overexpression of hsa_circ_0007843 promoted the invasion and migration of SW480 cells, whereas its downregulation suppressed their invasion and migration. Overexpression of hsa_circ_0007843 promoted tumor growth, whereas its downregulation inhibited tumor growth. We found that hsa_circ_0007843 interacted with miR-518c-5p and suppressed its expression, and miR-518c-5p interacted with matrix metallopeptidase 2 (MMP2) and promoted its expression and translation. Taken together, this study demonstrated that hsa_circ_0007843 acted as an miRNA sponge to regulate MMP2 expression by removing the inhibitory effect of miR-518c-5p on MMP2 gene translation, which further affected the invasive capability of SW480 cells.

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Circular RNA ciRS-7 Maintains Metastatic Phenotypes as a ceRNA of miR-1299 to Target MMPs

Cited by 79 publications

References 34 publications

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

CircSAMD4A regulates cell progression and epithelial‑mesenchymal transition by sponging miR‑342‑3p via the regulation of FZD7 expression in osteosarcoma

Hsa_Circ_0007843 Acts as a mIR-518c-5p Sponge to Regulate the Migration and Invasion of Colon Cancer SW480 Cells

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