MiR125a‐5p acting as a novel Gab2 suppressor inhibits invasion of glioma

Sun, Limei; Zhang, Baogang; Liu, Yuqing; Shi, Lihong; Liu, Hongli; Lu, Shaoying

doi:10.1002/mc.22256

Cited by 19 publications

(24 citation statements)

References 34 publications

(45 reference statements)

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“…For tumour suppressor genes, such as miR-125a-5p, the molecules are commonly hypermethylated in tumour tissues compared with non-tumour tissues. In addition to our study here, the miR-125a-5p has been demonstrated to be hypermethylated in glioma cells 27. Target gene screening and validation showed that the histone methyltransferase Suv39H1 was the miR-125a-5p target gene, which Suv39H1 is the miR-125a-5p target gene.…”

supporting

confidence: 64%

“…It has been demonstrated that some epigenetic modulators could modulate the miR‐125‐5p expression, such as HDACs (histone deacetylases),13, 25 or be modulated by miR‐125‐5p, such as Sirtuins 26. Furthermore, the putative promoter regions the miR‐125a‐5p are embedded in CpG islands and are hypermethylated in glioma cells 27. Considering the above findings, we wanted to test the expression and methylation status of miR‐125a‐5p in gastric cancer tissues and adjacent non‐tumour tissues and then to evaluate whether DNA methylation participates in regulating miR‐125a‐5p expression in human gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

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Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Cai

Chen

Shen

et al. 2018

J Cellular Molecular Medi

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Emerging evidence suggests that microRNAs (miRNAs) serve an important role in tumorigenesis and development. Although the low expression of miR‐125a‐5p in gastric cancer has been reported, the underlying mechanism remains unknown. In the current study, the low expression of miR‐125a‐5p in gastric cancer was verified in paired cancer tissues and adjacent non‐tumour tissues. Furthermore, the GC islands in the miR‐125a‐5p region were hypermethylated in the tumour tissues. And the hypermethylation was negatively correlated with the miR‐125a‐5p expression. Target gene screening showed that the histone methyltransferase Suv39H1 was one of the potential target genes. In vitro studies showed that miR‐125a‐5p could directly suppress the Suv39H1 expression and decrease the H3K9me3 levels. On the other hand, the Suv39H1 could induce demethylation of miR‐125a‐5p, resulting in re‐activation of miR‐125a‐5p. What is more, overexpessing miR‐125a‐5p could also self‐activate the silenced miR‐125a‐5p in gastric cancer cells, which suppressed cell migration, invasion and proliferation in vitro and inhibited cancer progression in vivo. Thus, we uncovered here that the epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer, suggesting that miR‐125a‐5p might be not only the potential prognostic value as a tumour biomarker but also potential therapeutic targets in gastric cancer.

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supporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Cai

Chen

Shen

et al. 2018

J Cellular Molecular Medi

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“…*P , 0.05, **P , 0.01. (51,52). In the present study, inhibitors of PI3K, MEK, or Jak2 significantly suppressed Gab2-mediated HepG2 cell proliferation and migration.…”

Section: Discussionsupporting

confidence: 57%

“…Moreover, Gab2 contributes to the angiogenic switch by increasing hypoxia-inducible factor-1α and VEGF levels in melanoma (29). In glioblastoma, both miRNA-197 and miR125a-5p inhibit glioma cell proliferation and invasion by negatively regulating Gab2 (51, 52). In the present study, inhibitors of PI3K, MEK, or Jak2 significantly suppressed Gab2-mediated HepG2 cell proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways

et al. 2017

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Our previous studies have found that Growth factor receptor-bound protein 2–associated binding protein 2 (Gab2)—a docking protein—governs the development of fatty liver disease. Here, we further demonstrate that Gab2 mediates hepatocarcinogenesis. Compared with a faint expression in para-carcinoma tissue, Gab2 was highly expressed in ∼60–70% of human hepatocellular carcinoma (HCC) specimens. Deletion of Gab2 dramatically suppressed diethylnitrosamine-induced HCC in mice. The oncogenic effects of Gab2 in HepG2 cells were promoted by Gab2 overexpression but were rescued by Gab2 knockdown. Furthermore, Gab2 knockout in HepG2 cells restrained cell proliferation, migration and tumor growth in nude mice. Signaling pathway analysis with protein kinase inhibitors demonstrated that oncogenic regulation by Gab2 in hepatic cells involved multiple signaling molecules, including ERK, Akt, and Janus kinases (Jaks), especially those that mediate inflammatory signaling. IL-6 signaling was increased by Gab2 overexpression and impaired by Gab2 deletion via regulation of Jak2 and signal transducer and activator of transcription 3 phosphorylation and the expression of downstream genes, such as Bcl-2 (B-cell lymphoma 2), c-Myc, MMP7 (matrix metalloproteinase-7), and cyclin D1 in vitro and in vivo. These data indicate that Gab2 mediates the pathologic progression of HCC by integrating multiple signaling pathways and suggest that Gab2 might be a powerful therapeutic target for HCC.—Cheng, J., Zhong, Y., Chen, S., Sun, Y., Huang, L., Kang, Y., Chen, B., Chen, G., Wang, F., Tian, Y., Liu, W., Feng, G.-S., Lu, Z. Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways.

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“…LIM kinase 1 (LIMK) is involved in the regulation of F-actin polymerization [11, 12]. F-actin dynamics is also regulated by the phosphorylating cofilin at Ser3, which is critical for cell chemotaxis and migration [13, 14]. Analysis of PlGF-1-induced phosphorylation of LIMK and cofilin in MDA231/miR-507 cells showed a marked inhibit activation of both cofilin and LIMK, compared with MDA231/NC cells, whereas both total LIMK and cofilin levels remained unchanged (Figure 3F).…”

Section: Resultsmentioning

confidence: 99%

MiR-507 inhibits the migration and invasion of human breastcancer cells through Flt-1 suppression

et al. 2016

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Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase-1 (VEGFR-1/Flt-1) is a tyrosine kinase receptor that binds placental growth factor (PlGF). Flt-1 is also highly expressed in breast-cancer tissues and breast-cancer cell lines. However, the molecular mechanism by which Flt-1 promotes breast-cancer invasion and metastasis by binding to PlGF-1 is unclear. In this study, we discovered that PlGF-1 and Flt-1 played a key role in the migration and invasion of breast cancer. Flt-1 promoted the migration and chemotaxis of breast-cancer cells by binding to PlGF-1. In addition, Flt-1 was confirmed to be a direct target gene of miR-507. miR-507 up-regulation inhibited the invasion and metastasis of breast-cancer cells in vitro and in vivo. Flt-1 overexpression rescued the invasion partially caused by the ectopic expression of miR-507. miR-507 expression in breast-cancer tissues and cell lines was lower than that in adjacent non-neoplastic tissues and normal cells. Clinical analysis indicated that miR-507 was negatively correlated with tumor differentiation, lymphatic metastasis, and the expression of Flt-1 in breast cancer. Furthermore, we showed that miR-507 down-regulation was due to the hypermethylation of its promotor region. Our results indicated that miR-507 represented potential therapeutic targets in breast cancer by modulating Flt-1.

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MiR125a‐5p acting as a novel Gab2 suppressor inhibits invasion of glioma

Cited by 19 publications

References 34 publications

Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways

MiR-507 inhibits the migration and invasion of human breastcancer cells through Flt-1 suppression

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