C/EBP-β-activated microRNA-223 promotes tumour growth through targeting RASA1 in human colorectal cancer

Sun, Da; Wang, C; Long, Songkai; Ma, Yingyu; Guo, Yu; Huang, Zhenping; Chen, Xiaojia; Zhang, C; Chen, J; Zhang, Jiahan

doi:10.1038/bjc.2015.107

Cited by 59 publications

(46 citation statements)

References 54 publications

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“…Thus, we hypothesized that RASA1 also participates in the pathogenesis of cardiac fibrosis. Previous studies showed that RASA1 is a target gene of miR-223 [17, 18]; however, whether miR-223 regulates RASA1 in CFs remains unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1

Liu¹,

Xu²,

Deng³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Percutaneous coronary intervention reduces acute myocardial infarction (MI)-induced mortality to a great extent, but effective treatments for MI-induced cardiac fibrosis and heart failure are still lacking. MicroRNAs (miRNAs) play a variety of roles in cells and have thus been investigated extensively. MicroRNA-223 (miR-223) expression has been reported to be altered in post-MI heart failure in humans; however, the roles of miR-223 in MI remain unknown. Our study aimed to elucidate the roles of miR-223 in cardiac fibrosis. Methods: Cultured cardiac fibroblasts (CFs) were activated by TGF-β1 stimulation. Gain and loss of miR-223 and RAS p21 protein activator 1 (RASA1) knockdown in CFs were achieved by transfecting the cells with miR-223 mimics and inhibitors, as well as small interfering RNA-RASA1 (siRASA1), respectively. Quantitative real-time reverse transcriptase-polymerase chain reactions (qRT-PCR) was used to determine miR-223-3p and RASA1 expression levels, and Cell Counting Kit-8 (CCK-8), transwell migration and scratch assays were performed to assess CFs viability and migration, respectively. Western blotting was used to detect collagen I, collagen III, alpha-smooth muscle actin (a-SMA), RASA1, p-Akt/t-Akt, p-MEK1/2/t-MEK1/2, and p-ERK1/2/t-ERK1/2 protein expressions, and immunofluorescence assays were used to detect the expression of α-actin, vimentin and α-SMA. Luciferase assays were carried out to determine whether miR-223 binds to RASA1. Rat models of MI were established by the ligation of the left anterior descending (LAD) coronary artery. MiR-223 inhibition in vivo was achieved via intramyocardial injections of the miR-223 sponge carried by adeno-associated virus 9 (AAV9). The cardiac function was detected by echocardiography, and cardiac fibrosis was shown by Masson’s trichrome staining. Results: miR-223 was increased in CFs compared to cardiomypcytes, and TGF-β1 treatment increased miR-223 expression in CFs. The miR-223 mimics enhanced cell proliferation and migration and collagen I, collagen III, and α-SMA protein expression in CFs, while the miR-223 inhibitors had contrasting effects and partially prevented the promoting effects of TGF-β1. qRT-PCR and western blotting revealed that miR-223 negatively regulated RASA1 expression, and the luciferase assays showed that miR-223 suppressed the luciferase activity of the RASA1 3’ untranslated region (3'UTR), indicating that miR-223 binds directly to RASA1. Similar to transfection with the miR-223 mimics, RASA1 knockdown enhanced cell proliferation and migration and collagen I, collagen III, and α-SMA protein expression in CFs. Moreover, RASA1 knockdown partially reversed the inhibitory effects of the miR-223 inhibitor on cell proliferation and migration and collagen I, collagen III, and α-SMA protein expression, indicating that the effects of miR-223 in CFs are partially mediated by the regulation of RASA1 expression. Further exploration showed that miR-223 mimics and siRASA1 promoted MEK1/2, ERK1/2 and AKT phosphorylation, while the mi...

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Section: Introductionmentioning

confidence: 99%

MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1

Liu¹,

Xu²,

Deng³

et al. 2018

Cell Physiol Biochem

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“…The cell proliferation assay was performed as previously described44. Briefly, Saos-2 or MNNG/HOS cells with over-expression or knocked down-expression of miR-199a-5p were seeded onto 96-well plates at a density of 6 × 10 3 cells per well.…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed as previously described44. Protein extracts of cells and tissues were prepared using RIPA lysis buffer (Sigma-Aldrich), and the total protein content was quantified by the BCA protein assay kit (Thermo Scientific, Rockford, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma

Wang

Guo

et al. 2017

Sci Rep

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Osteosarcoma (OS) is the most common primary bone malignancy and remains a leading cause of cancer-related deaths in adolescents. Emerging evidence indicates that microRNAs (miRNAs) are correlated with clinical and biological characteristics of OS. However, the involvement of miR-199a-5p in OS development remains unclear. In this study, we examined the function of miR-199a-5p in vitro and in vivo. The results showed that miR-199a-5p was significantly up-regulated in OS patient tissues and cells. The inhibition of miR-199a-5p led to a significant decrease in cell proliferation and tumour growth. We further demonstrated that miR-199a-5p could directly bind to the 3′UTRs of the mRNA of both PIAS3 and p27 and mediate a decrease in the protein levels of PIAS3 and p27, thereby stimulating STAT3 activation and cell cycle progression in OS cells. Rescue experiments of PIAS3 and p27 further revealed that PIAS3 and p27 were functional targets of miR-199a-5p. Moreover, enhancing the expressions of both PIAS3 and p27 using miR-199a-5p-targeted inhibitors in an OS xenograft model was shown to be a promising approach for OS clinical therapy. Our findings indicate that the pathway of miR-199a-5p targeting both PIAS3 and p27 is a possible mechanism that contributes to tumour growth in OS.

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“…Also suggestive is the importance of microRNAs miR‐31 and miR‐223, which seem to share a common stimulatory mechanism in CRC proliferation. In this context, C/EBP‐β becomes important as a positive effector of miR‐223 expression . Thus, the attenuating effect of melatonin on the C/EBP‐β cascade would decrease miR‐223 expression, leading finally to prevent the progression of CRC.…”

Section: Multimodal Approach Using Melatonin Against Progression and mentioning

confidence: 99%

“…On the one hand, C/EBP‐β has been found strongly upregulated in CRC, and CRC cells showed reduced invasiveness and malignant potential when transplanted into C/EBP‐β deficient animals . Also suggestive is the importance of microRNAs miR‐31 and miR‐223, which seem to share a common stimulatory mechanism in CRC proliferation. In this context, C/EBP‐β becomes important as a positive effector of miR‐223 expression .…”

Section: Multimodal Approach Using Melatonin Against Progression and mentioning

confidence: 99%

The emergence of melatonin in oncology: Focus on colorectal cancer

Gil‐Martín

Egea

Reíter

et al. 2019

Medicinal Research Reviews

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Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy‐treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Because of its epidemiological importance and symptomatic debut in advanced stages of difficult clinical management, colorectal cancer (CRC) is a preferential target for testing new therapies. In this regard, the development of effective forms of clinical intervention for the improvement of CRC outcome, specifically metastatic CRC, is urgent. At the same time, the need to reduce the costs of conventional anti‐CRC therapy results is also imperative. In light of this status quo, the therapeutic potential of melatonin, and the direct and indirect critical processes of CRC malignancy it modulates, have aroused much interest. To illuminate the imminent future on CRC research, we focused our attention on the molecular mechanisms underlying the multiple oncostatic actions displayed by melatonin in the onset and evolution of CRC and summarized epidemiological evidence, as well as in vitro, in vivo and clinical findings that support the broadly protective potential demonstrated by melatonin.

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C/EBP-β-activated microRNA-223 promotes tumour growth through targeting RASA1 in human colorectal cancer

Cited by 59 publications

References 54 publications

MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1

MicroRNA-223 Regulates Cardiac Fibrosis After Myocardial Infarction by Targeting RASA1

MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma

The emergence of melatonin in oncology: Focus on colorectal cancer

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