MicroRNA-26a Inhibits Angiogenesis by Down-Regulating VEGFA through the PIK3C2α/Akt/HIF-1α Pathway in Hepatocellular Carcinoma

Chai, Zong‐Tao; Kong, Jian; Zhu, Xiao‐Dong; Zhang, Yuanyuan; Lu, Lu; Zhou, Jiamin; Wang, Longrong; Zhang, Kezhi; Zhang, Qiangbo; Ao, Jian‐Yang; Wang, Miao; Wu, Wei‐Zhong; Tang, Zhao–You; Sun, Hui‐Chuan

doi:10.1371/journal.pone.0077957

Cited by 104 publications

(87 citation statements)

References 50 publications

(57 reference statements)

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“…Bevacizumab, a specific anti-VEGF drug that has led to over survival times of about 24 months when combined with standard chemotherapy regimens compared with about 20 months when treated with standard chemotherapy alone [29,30]. Some VEGFA-targeted miRNAs including miR-203 [31], miR-497 [32], miR-26a [33], and miR-199a-5p [34] have According to several algorithms, we predicted that miR-140-5p may directly target VEGFA. Using a dual-luciferase reporter assay we showed that miR-140-5p directly bound to the 3'UTR of VEGFA, which contains a miR-140-bingding site.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

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Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

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“…Consistently, miR-26a attenuated cell proliferation and impaired cell cycle progression by targeting the Polycomb complex protein EZH2 in association with lymphomagenesis [47]. MiR-26a was shown to play a role in angiogenesis in HCC through its effect on the PI3K-C2α/Akt/VEGF signaling pathway [16]. Ectopic expression of miR-26a downregulated VEGFA and impaired migration and tube formation in human umbilical vein endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have indicated cell type-specific effects of miR-26a on neovascularization. While miR-26a promotes tumor angiogenesis in glioma [15], miR-26a expression significantly suppressed in vivo tumor-associated angiogenesis in HCC [14,16]. Interestingly, ectopic expression of miR-26a markedly induced endothelial cell cycle arrest and inhibited ECs migration, sprouting angiogenesis, and network tube formation in matrigel in vitro and in vivo [17].…”

Section: Introductionmentioning

confidence: 99%

A Dysregulated MicroRNA-26a/EphA2 Axis Impairs Endothelial Progenitor Cell Function via the p38 MAPK/VEGF Pathway

Zuo

Zhi

Zhang

et al. 2015

Cell Physiol Biochem

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Background: Dysfunction of circulating endothelial progenitor cells (EPCs) is associated with the onset of cardiovascular disorders. Circulating microRNAs (miRNAs) have been recognized as novel biomarkers and potential therapeutic targets. Here, we examined the role of miR-26a overexpression in atherosclerosis and explored the underlying mechanisms. Methods: EPCs were obtained from patients with atherosclerosis and healthy controls. Bone marrow (BM)-derived EPCs were exposed to hypoxia to mimic the atherosclerotic environment and miR-26a, EphA2 and p38 MAPK levels were measured by qRT-PCR and western blotting, and VEGF levels were determined by enzyme linked immunosorbent assay. Cell viability was assessed using the MTT assay, and luciferase activity assays confirmed EphA2 as a target of miR-26a. Results: MiR-26a was overexpressed in patients with atherosclerosis and associated with EPC dysfunction. EphA2 was identified as a direct target of miR-26a. Overexpression of miR-26a downregulated EphA2 and impaired EPC function, whereas knockdown of miR-26a upregulated EphA2 and reversed hypoxia-induced EPC dysfunction. MiR-26a overexpression or knockdown modulated the activity of p38 MAPK and the levels of VEGF in EPCs. Conclusions: The role of miR-26a in atherosclerosis is mediated by its target EphA2 via a mechanism involving the p38 MAPK/VEGF pathway.

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“…However, the activity and regulatory mechanisms of miR-18a are not fixed across various pathological and physiological conditions, or in different types of tumors, and factors that are associated with invasive meningiomas are not limited to HIF-1α (23)(24)(25). In addition, there are abundant miRNAs that may potentially regulate these factors.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-18a regulates invasive meningiomas via hypoxia-inducible factor-1α

Gao

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to investigate the effects of microRNA-18a (miR-18a) on the invasiveness and metastasis of invasive meningiomas and the underlying mechanism. A total of 69 patients with meningiomas (30 patients in the invasive meningioma group and 39 patients in the non-invasive meningioma group) and 48 cases in the control group were enrolled. Samples of meningioma tissues, serum and cerebrospinal fluid were collected. Reverse transcription-quantitative polymerase chain reaction was performed to quantify the expression levels of hypoxia-inducible factor-1α (HIF-1α) mRNA and miR-18a. Western blot analysis was used to determine protein expression levels of HIF-1α. The expression levels of HIF-1α mRNA and protein in all three types of sample from the invasive meningioma group were significantly higher compared with those in the control and non-invasive meningioma groups (P<0.05), and the expression levels of HIF-1α mRNA in the serum and cerebrospinal fluid of the non-invasive meningioma group were significantly higher compared with those in the control group (P<0.05). The expression levels of miR-18a in the invasive meningioma group were significantly reduced compared with those in the control and non-invasive meningioma groups (P<0.05), whereas the levels of miR-18a in the non-invasive meningioma group were significantly lower compared with those in the control group (P<0.05). The expression of HIF-1α is significantly upregulated in patients with invasive meningiomas, possibly due to the downregulation of miR-18a expression. Therefore, miR-18a may regulate invasive meningiomas via HIF-1α.

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MicroRNA-26a Inhibits Angiogenesis by Down-Regulating VEGFA through the PIK3C2α/Akt/HIF-1α Pathway in Hepatocellular Carcinoma

Cited by 104 publications

References 50 publications

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

A Dysregulated MicroRNA-26a/EphA2 Axis Impairs Endothelial Progenitor Cell Function via the p38 MAPK/VEGF Pathway

MicroRNA-18a regulates invasive meningiomas via hypoxia-inducible factor-1α

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