Epigenetic silencing of miR-130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling

Gao, Feng; Wang, Fagang; Liu, Renrong; Xue, Feng; Zhang, Jian; Xu, Guangqi; Bi, Jianhai; Meng, Zhen; Huo, Ran

doi:10.3892/ijo.2017.3943

Cited by 20 publications

(15 citation statements)

References 40 publications

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“…Our previous data revealed the negative regulation of TFPI‐2 by promoter methylation, although this could not arbitrarily exclude the involvement of another regulatory mechanism in this setting . Therefore, we aimed to identify the potential miRs that convergently inhibited the expression of TFPI‐2 in gastric cancer.…”

Section: Resultsmentioning

confidence: 95%

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Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Geng

Liu

et al. 2020

The Journal of Gene Medicine

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Background:The tumor suppressor role of tissue factor pathway inhibitor 2 (TFPI-2) has been reported in various tumors. The present study aimed to improve the understanding of the oncogenic properties of TFPI-2 in gastric cancer. Methods:Relative expression of TFPI-2 was determined by a real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell viability was measured via a cell counting kit-8 assay and proliferation was evaluated by a colony formation assay. Cell apoptosis was assessed with a caspase-3 activity kit and invasion was evaluated by a transwell chamber assay. The methylation level of TFPI-2 promoter was assayed by methylation-specific PCR. The regulatory effect of miR-27a-3p on TFPI-2 was analyzed with a luciferase reporter assay. The direct association between miR-27a-3p and TFPI-2 was shown by biotin-labelling pulldown.Results: TFPI-2 was down-regulated in gastric cancer, which associated with an unfavorable prognosis clinically. Ectopic introduction of TFPI-2 greatly compromised cell viability, colony formation and invasive capacity, and also induced cell apoptosis simultaneously. The promoter region of TFPI-2 was extensively methylated in gastric cancer tissues compared to normal tissues, suggesting the epigenetic inhibition of TFPI-2 expression. We further identified that TFPI-2 functioned as sponge RNA against miR-27a-3p. Most importantly, miR-27a-3p-specific inhibitor significantly exerted a tumor suppressor function akin to TFPI-2 itself, and the anti-tumoral activities were completely abolished by TFPI-2 knockdown. Conclusions:We found that the epigenetically suppressed TFPI-2 compromised sponging effects with respect to miR-27a-3p in gastric cancer, which consequently and mechanistically contributed to the tumor biology of gastric cancer. K E Y W O R D Sgastric cancer, methylation, miR-27a-3p, TFPI-2 Geng and Liu contributed equally to this work.

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Section: Resultsmentioning

confidence: 95%

“…suggested that miR‐616‐3p promoted cell proliferation and migration via modulating the expression of TFPI‐2 in preeclampsia. Gao et al . demonstrated that miR‐130a was subjected to epigenetic silencing in hemangioma, which consequently ameliorated the malignancy through targeting TFPI‐2 via the FAK/PI3K/Rac1/mdm2 signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Geng

Liu

et al. 2020

The Journal of Gene Medicine

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“…MiR‐130a inhibitor represses the growth and angiogenesis of haemangioma by targeting tissue factor pathway inhibitor 2 (TFPI2) via inhibiting the focal adhesion kinase (FAK)/phosphoinositide 3‐kinase (PI3K)/Rac1/anti‐mouse double minute (mdm2) signalling pathway 108. In addition, the inhibition of miR‐130a represses cell proliferation, migration and angiogenesis in gastric cancer by enhancing runt‐related transcription factor 3 (RUNX3) protein expression 109.…”

Section: Mirnas Regulated By Pro‐or Anti‐angiogenesis Factors or Hypomentioning

confidence: 99%

The regulatory role of microRNAs in angiogenesis‐related diseases

Sun

Lei

et al. 2018

J Cellular Molecular Medi

116

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MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression at a post‐transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis‐related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA‐based biomarkers in the diagnosis, treatment and prognosis of angiogenesis‐related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

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“…In addition to the lncRNAs, microRNAs (miRNAs), a subgroup of ncRNAs with about 20 nucleotides that inhibit their target gene are differentially expressed in different phase HAs [19]. Some studies showed that miR-143, miR-199a and miR-130a are involved in regulating cell proliferation and invasion in HAs cells [20][21][22]. Nevertheless, little is known about the functions and underlying mechanisms of MEG3 in the pathogenesis HAs.…”

Section: Introductionmentioning

confidence: 99%

lncRNA MEG3 Suppresses the Tumorigenesis of Hemangioma by Sponging miR-494 and Regulating PTEN/ PI3K/AKT Pathway

Dai

Wan

Qiu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dysregulation of long noncoding RNAs (lncRNAs) is associated with the proliferation and metastasis in a variety of cancers, of which lncRNA maternally expressed gene 3 (MEG3) has been indicated as a tumor suppressor in multiple malignancies. However, the underlying mechanisms by which MEG3 contributes to human hemangiomas (HAs) remain undetermined. Methods: qRT-PCR analysis was performed to examine the expression levels of MEG3 and VEGF in proliferating or involuting phase HAs. MTT, colony formation assay, flow cytometry analysis and a subcutaneous xenograft tumor model were conducted to assess the effects of MEG3 on the HAs tumorigenesis. The interaction between MEG3 and miRNAs or their downstream pathways was evidenced by bioinformatic analysis, luciferase report assays, RNA immunoprecipitation (RIP) assay. and Western blot analysis. Results: The expression of MEG3 was substantially decreased and had a negative correlation with VEGF expression in proliferating phase HAs, as compared with the involuting phase HAs and normal skin tissues. Ectopic expression of MEG3 suppressed cell proliferation, colony formation and induced cycle arrest in vitro and in vivo, followed by the downregulation of VEGF and cyclinD1, but knockdown of MEG3 reversed these effects. Furthermore, MEG3 was verified to act as a sponge of miR-494 in HAs cells, and miR-494 counteracted MEG3-caused anti-proliferative effects by regulating PTEN/PI3K/AKT pathway, and exhibited the negative correlation with MEG3 and PTEN expression in proliferating phase HAs. Conclusion: Our findings suggested that lncRNA MEG3 inhibited HAs tumorigenesis by sponging miR-494 and regulating PTEN/PI3K/AKT pathway.

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Epigenetic silencing of miR-130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling

Cited by 20 publications

References 40 publications

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

The regulatory role of microRNAs in angiogenesis‐related diseases

lncRNA MEG3 Suppresses the Tumorigenesis of Hemangioma by Sponging miR-494 and Regulating PTEN/ PI3K/AKT Pathway

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