Downregulation of miR-126 induces angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer

Sasahira, Tomonori; Kurihara, Miyako; Bhawal, Ujjal K.; Ueda, Naonori; Shimomoto, Takasumi; Yamamoto, Kazuhiko; Kirita, Tadaaki; Kuniyasu, Hiroki

doi:10.1038/bjc.2012.330

Cited by 177 publications

(122 citation statements)

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“…For example, miRNA (miR)-126, originally identified as an endothelial-specific miRNA playing an essential role in angiogenesis and vascular integrity, [9][10][11] has been shown to function as a critical tumor suppressor in various types of solid tumors. 5,[12][13][14][15][16][17][18][19] In contrast, we have shown that miR-126 is aberrantly overexpressed and likely plays an oncogenic role in core binding factor (CBF) leukemia. 20 CBF leukemia is characterized by the presence of a t(8;21)(q22;q22) or an inv(16)(p13.1q22) chromosomal rearrangement, which accounts for ;20% to 30% of primary acute myeloid leukemia (AML) cases.…”

Section: Key Pointsmentioning

confidence: 88%

Overexpression and knockout of miR-126 both promote leukemogenesis

Chen

et al. 2015

Blood

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Key Points• Both overexpression and knockout of miR-126 result in enhanced leukemogenesis.• Overexpression and knockout of miR-126 activate distinct gene signaling and are associated with different biological consequences.It is generally assumed that gain-and loss-of-function manipulations of a functionally important gene should lead to the opposite phenotypes. We show in this study that both overexpression and knockout of microRNA (miR)-126 surprisingly result in enhanced leukemogenesis in cooperation with the t(8;21) fusion genes AML1-ETO/RUNX1-RUNX1T1 and AML1-ETO9a (a potent oncogenic isoform of AML1-ETO). In accordance with our observation that increased expression of miR-126 is associated with unfavorable survival in patients with t(8;21) acute myeloid leukemia (AML), we show that miR-126 overexpression exhibits a stronger effect on long-term survival and progression of AML1-ETO9a-mediated leukemia stem cells/leukemia initiating cells (LSCs/LICs) in mice than does miR-126 knockout. Furthermore, miR-126 knockout substantially enhances responsiveness of leukemia cells to standard chemotherapy. Mechanistically, miR-126 overexpression activates genes that are highly expressed in LSCs/LICs and/or primitive hematopoietic stem/progenitor cells, likely through targeting ERRFI1 and SPRED1, whereas miR-126 knockout activates genes that are highly expressed in committed, more differentiated hematopoietic progenitor cells, presumably through inducing FZD7 expression. Our data demonstrate that miR-126 plays a critical but 2-faceted role in leukemia and thereby uncover a new layer of miRNA regulation in cancer. Moreover, because miR-126 depletion can sensitize AML cells to standard chemotherapy, our data also suggest that miR-126 represents a promising therapeutic target. (Blood. 2015;126(17):2005-2015 Introduction MicroRNAs (miRNAs) have been implicated in the pathogenesis of various types of cancers. [1][2][3][4][5][6][7][8] Some miRNAs play distinct roles in different types of cancers. For example, miRNA (miR)-126, originally identified as an endothelial-specific miRNA playing an essential role in angiogenesis and vascular integrity, [9][10][11] has been shown to function as a critical tumor suppressor in various types of solid tumors. 5,[12][13][14][15][16][17][18][19] In contrast, we have shown that miR-126 is aberrantly overexpressed and likely plays an oncogenic role in core binding factor (CBF) leukemia. 20 CBF leukemia is characterized by the presence of a t(8;21)(q22;q22) or an inv(16)(p13.1q22) chromosomal rearrangement, which accounts for ;20% to 30% of primary acute myeloid leukemia (AML) cases. [21][22][23] The potential oncogenic role of miR-126 in AML was further confirmed by other groups. 24,25 However, it was reported that attenuation of miR-126 expression in normal hematopoietic stem/progenitor cells (HSPCs) resulted in expansion of long-term repopulating hematopoietic stem cells. 26 Thus, the definitive role of miR-126 in the hematopoietic system warrants further investigation.To precisely define ...

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Section: Key Pointsmentioning

confidence: 88%

Overexpression and knockout of miR-126 both promote leukemogenesis

Chen

et al. 2015

Blood

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“…OSCC often leads to dysfunctions of chewing, swallowing, speech as well as the loss of esthetics. What's more, although there are more than 80% of early-stage OSCC patients that can be cured by therapy, there are still about 70% of patients with progressive disease cannot be cured [4]. Consequently, it is urgently needed for precise early detection of OSCC patients.…”

Section: Introductionmentioning

confidence: 99%

The role of survivin in oral squamous cell carcinoma

Liang¹,

Guo²,

Liu³

2018

biomedicalresearch

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Tumor samples were collected from 30 patients who were suffered with squamous cell carcinoma of the oral cavity. The patients were treated by radical surgical resection between 2012 and 2015 at the Jinling hospital. There were 24 patients who were positive for survivin (80.0%) and 6 patients who were negative for survivin (20.0%). Compared with normal mucosa, there were significantly up-regulated survivin and caspase 9 in OSCC which were proved by Flow Cytometry (FCM) and western blot, respectively. In conclusion, survivin and Caspase 9 might be prognostic markers for Oral Squamous Cell Carcinoma (OSCC).

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“…Several online databases are available to identify potential miRNA targets. Analysis preformed using the PicTar algorithm (http://www.pictar.org/) (20), miRBase (www.mirbase.org) (21) and TargetScan target prediction (version 6.2; www.targetscan.org) (22) tools revealed that VEGF was the putative target of miR-126 that may serve a role in angiogenesis owing to regulation of VEGF signaling (23,24). Alteration of expression of miR-126 was also reported in various breast, lung and prostate cancer cells (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor

et al. 2018

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Abstract. Primary ovarian cancer is the main cause of gynecological cancer-associated mortality. However, the mechanism behind the spread of ovarian cancer requires elucidation. The present study aimed to investigate the effects of microRNA-126 (miR-126) on differentiation and invasion, and its mechanism in primary ovarian cancer. Ovarian cancer SKOV3 cells transfected with LV3-has-miR-126 mimics and LV3-has-miR-126 inhibitor were produced; it was revealedthatLV-miR-126 mimics could induce cell cycle arrest at G 1 phase, suppress cell invasion through Matrigel-coated membranes and downregulate the expression of vascular endothelial growth factor (VEGF). Furthermore, LV-has-miR-126 inhibitor-transfected cells could increase the number of cells in S phase, induce cell invasion and upregulate the expression of VEGF. The present study, to the best of our knowledge, is the first to report that miR-126 may serve tumor suppressor roles by inducing G 1 cell cycle arrest and suppressing invasion in ovarian cancer cells, at least in part by targeting VEGF expression.

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Downregulation of miR-126 induces angiogenesis and lymphangiogenesis by activation of VEGF-A in oral cancer

Cited by 177 publications

References 49 publications

Overexpression and knockout of miR-126 both promote leukemogenesis

Overexpression and knockout of miR-126 both promote leukemogenesis

The role of survivin in oral squamous cell carcinoma

MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor

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