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

Luo, Jun; Zhu, Caidan; Wang, Hongya; Li, Yu; Zhou, Jianwei

doi:10.3892/ol.2018.8025

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…Moreover, we found that the low miR-126 expression in OC tissues was related to the aggressive progression of OC patients. In addition, miR-126 overexpression suppressed OC cell proliferation, migration and invasion capability, which was inconsistent with a previous report that miR-126 affected OC cell differentiation and invasion ( 48 ).…”

Section: Discussioncontrasting

confidence: 99%

MicroRNA‑126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial‑to‑mesenchymal transition and ERK/MAPK signaling pathway

et al. 2020

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Ovarian cancer (OC) is a common gynecological malignant carcinoma worldwide. Accumulating research has revealed that multiple microRNAs (miRNAs) are abnormally expressed at different levels in various malignancies, playing vital roles in tumorigenesis. This study investigated the regulatory functions and potential mechanism of miR-126 in OC proliferation, invasion and migration. It was found that miR-126 was prominently downregulated in OC. Moreover, the decrease of miR-126 promoted the aggressive phenotypes and indicated poor prognosis of OC patients. Functional assays demonstrated that restoration of miR-126 dramatically repressed OC cell proliferation, migration and invasion. Furthermore, luciferase reporter assay was conducted to verify putative binding sites of miR-126 in the epidermal growth factor-like domain 7 (EGFL7) 3 untranslated region (3′UTR), indicating that EGFL7 was a target gene of miR-126 in OC cells. It was further discovered that miR-126 exerts its function on regulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT) in OC cells. The above findings suggested that miR-126 served as a cancer suppressor in OC, suggesting a promising application of miR-126 in the clinical diagnosis and therapeutics of OC.

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Section: Discussioncontrasting

confidence: 99%

MicroRNA‑126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial‑to‑mesenchymal transition and ERK/MAPK signaling pathway

et al. 2020

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“…Moreover, Chip-based profiling needs to be validated on a platform with more specificity. Previous studies have relied on established cell lines (13,21), which cannot simulate clinical carcinomas in a perfect manner. Cell lines, for example, accumulate genetic alterations in culture.…”

Section: Discussionmentioning

confidence: 99%

miR‑126 regulates the progression of epithelial ovarian cancer in vitro and in vivo by targeting VEGF‑A

Liu

Huang

et al. 2020

Int J Oncol

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has been shown to be associated with ovarian cancer in previous studies. In ovarian cancer, however, the specific status of miR-126 remains largely unknown. In the present study, to clarify its role in ovarian cancer, the levels of miR-126 were first examined using laser microdissection and RT-qPCR. It was found that the miR-126 level was decreased in ovarian tissue samples and the restoration of miR-126 inhibited cell proliferation, cell invasion and migration in vitro and suppressed tumor growth in vivo. A bioinformatics search revealed that the angiogenesis-related gene, vascular endothelial growth factor (VEGF)-A, was among the potential targets of miR-126. The suppression of invasion and proliferation induced by ectopic miR-126 expression was nullified by the ectopic expression of VEGF-A, suggesting that these suppressive effects were largely attributable to the ability of miR-126 to target VEGF-A. Moreover, the restoration of miR-126 suppressed the angiogenic potential of human umbilical vein endothelial cells (HUVECs). On the whole, these findings indicate that the loss of expression of miR-126 contributes to the abnormal VEGF-A accumulation and subsequent unchecked cell invasion and cell proliferation in epithelial ovarian cancer.

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“…This is in line with previous studies, where overexpression of miR-126 mimics causes a downregulation of VEGF in ovarian, hepatocellular, and lung cancer. [27][28][29][30] With the cancer pathway finder, testing 9 different cancer pathways included total 84 specific genes, we found that only MAP kinase (MEK1) and DNA damage (POLB and TERF1) genes were slightly though significantly affected by miR-126 overexpression in univariable analysis. Interestingly, a recent study showed that miR-126 (mimic) increases telomere length, consistent with the observed increase of TERF1 gene expression in EO33 cells (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Tumor microRNA-126 controls cell viability and associates with poor survival in patients with esophageal adenocarcinoma

Toxopeus

Lynam‐Lennon

Biermann

et al. 2019

Exp Biol Med (Maywood)

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Esophageal adenocarcinoma displays a poor prognosis and current treatments are often not curative. Pathological TNM-stage is a prognostic parameter, but a better understanding of the pathophysiology of esophageal adenocarcinoma is needed to better predict survival. Recent work in other malignancies indicated an important role for the regulator microRNA-126 (miR-126) in tumors. The aim of this study was to investigate the function of miR-126 in esophageal adenocarcinoma and to correlate expression of miR-126 with tumor cell behavior and patient survival. Functional assays were performed in esophageal adenocarcinoma cell lines (OE33) in vitro by overexpressing or antagonizing miR-126 and assessing cellular processes linked to the hallmarks of cancer. In vivo pre-treatment biopsies of 58 patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiotherapy and surgery were analyzed for miR-126 expression in tumor cells by qRT-PCR and patient survival was analyzed by Kaplan–Meier and Cox regression. In OE33 cancer cells, stable overexpression of miR-126 modest though significantly altered expression of genes related to cell death (MEK1) and DNA repair (POLB and TERF1) was observed. Also the secretion of the angiogenic and pro-inflammatory factors, VEGF, IL-1β, and IL-6 were regulated by miR-126 ( P < 0.029). Importantly, miR-126 was found to be a regulator of cell viability in OE33 cells. Overexpressing ( P = 0.043) and antagonizing ( P = 0.035) miR-126 showed reciprocal effects on tumor cell viability and significantly regulated expression of pro- and anti-apoptotic genes, TP53, and GATA6 ( P < 0.031). In patients, high levels of miR-126 expression in pre-treatment tumors were significantly associated with poor survival ( P = 0.031). In multivariable analysis, high miR-126 ( P = 0.038) together with ypN-stage ( P = 0.048) were shown to be independent risk factors for poor survival. In conclusion, high expression of miR-126 in esophageal adenocarcinoma prevents tumor-cell death and is associated with poor patient survival. This study warrants further analysis of miR-126 as biomarker or potential therapeutic target for OAC. Impact statement Esophageal adenocarcinoma is a common form of cancer of the esophagus. It has an increasing health impact as it is associated with very poor patient survival. A better understanding of the pathophysiology of this cancer is needed to identify better treatment strategies and to provide a better prognosis for these patients. MicroRNAs have emerged as important molecular regulators of cancer cell viability and proliferation. The aim of our study was to investigate the role of one very well established microRNA, miR-126, in esophageal adenocarcinoma. Our research shows clear experimental evidence that miR-126 controls cell viability of esophageal adenocarcinoma cells. High (over)expression of miR-126 increased the viability of these cells. Our preclinical data were shown to be clinically relevant for this field of oncology. In an independent validation study of esophageal adenocarcinoma biopsies, we confirmed that high miR-126 expression in tumor cells was an independent risk factor for poor patient survival.

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

Cited by 8 publications

References 37 publications

MicroRNA‑126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial‑to‑mesenchymal transition and ERK/MAPK signaling pathway

MicroRNA‑126 exerts antitumor functions in ovarian cancer by targeting EGFL7 and affecting epithelial‑to‑mesenchymal transition and ERK/MAPK signaling pathway

miR‑126 regulates the progression of epithelial ovarian cancer in vitro and in vivo by targeting VEGF‑A

Tumor microRNA-126 controls cell viability and associates with poor survival in patients with esophageal adenocarcinoma

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