Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells

Saito, Yoshimasa; Friedman, Jeffrey M.; Chihara, Yoshitomo; Egger, Gerda; Chuang, Jody C.; Liang, Gangning

doi:10.1016/j.bbrc.2008.12.098

Cited by 213 publications

(162 citation statements)

References 21 publications

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“…When comparing EGFL7 and miR126 VA (adjacent sections), we detected a positive, significant relationship in biopsies and tumor resections, respectively, indicating some degree of common transcriptional regulation of miR126 and EGFL7. This is not surprising, because transcription of the EGFL7 gene also involves transcription of miR126 (22)(23)(24).…”

Section: Discussionmentioning

confidence: 96%

Epidermal Growth Factor–like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

Hansen

Nielsen

Sørensen

et al. 2014

Molecular Cancer Therapeutics

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The number of approved antiangiogenic drugs is constantly growing and emphasizes the need for predictive biomarkers. The aim of this study was to analyze the predictive value of epidermal growth factor-like domain 7 (EGFL7) and microRNA-126 (miR126) to first-line chemotherapy combined with bevacizumab, in patients with metastatic colorectal cancer (mCRC). A total of 158 patients from two different, but comparable, cohorts were included. Analyses were performed on tumor tissue from the primary tumor either based on a whole-tumor resection or an endoscopic biopsy. EGFL7 was analyzed by immunohistochemistry (IHC) and miR126 by in situ hybridization (ISH). Both biomarkers were quantified by image-guided analyses. Endpoints were response rate (RR) and progression-free survival (PFS). The EGFL7 vessel area (VA) in tumor resections was closely related to treatment response with a median EGFL7 VA in responding patients of 4 [95% confidence interval (CI), 4-6] compared with 8.5 (95% CI, 7-11) in nonresponders, P ¼ 0.0008. This difference translated into a borderline significant difference in PFS (P ¼ 0.06). Furthermore, a significant relationship between high EGFL7 VA and KRAS mutation was detected (P ¼ 0.049). The results showed no significant relationship between the miR126 VA and the clinical endpoints. Our study suggests a predictive value of EGFL7 in regard to first-line chemotherapy and bevacizumab in patients with mCRC and supports the mechanism of a dual blocking of the vascular endothelial growth factor-A and EGFL7 axis in this setting. Mol Cancer Ther; 13(9); 2238-45. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 96%

Epidermal Growth Factor–like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

Hansen

Nielsen

Sørensen

et al. 2014

Molecular Cancer Therapeutics

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“…However, similar to our study they proposed a regulatory role for miR-126 in inflammation, specifically in the vasculature. Saito et al (12) have recently reported that downregulation of miR-126 can be induced by inhibitors of DNA methylation and histone deacetylation.…”

Section: Discussionmentioning

confidence: 99%

“…miR-126 is 21 nucleotides in length, located on chromosome 9q34.3 and is contained within intron 5 of its host gene epidermal growth factor like-7 (6,9). In recent studies, miR-126 has been shown to have functional roles in angiogenesis (10,11), to be *Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital; and † Cancer Genetics Group, Royal College of Surgeons in Ireland, Dublin, Ireland downregulated in a number of malignancies (8,12) and to act as a tumor suppressor in breast cancer (13). In silico analysis of a number of miRNA target prediction databases shows that TOM1 is a potential target of miR-126.…”

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confidence: 99%

miR-126 Is Downregulated in Cystic Fibrosis Airway Epithelial Cells and Regulates TOM1 Expression

Oglesby

Bray

Chotirmall

et al. 2010

The Journal of Immunology

171

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“…However, the functions of miR-126 in cancers appear to be diverse and remain largely unknown. miR-126 was reported to be downregulated and to act as a tumor suppressor in different cancers of the lung (10,11), stomach (12,13), cervix (14), bladder and prostate (15). miR-126 was also significantly downregulated in ectopic endometria (EC) versus eutopic endometria (EU), suggesting that it may play an initial role in the development and progression of endometriosis (Ems) (16).…”

Section: Introductionmentioning

confidence: 99%

miR-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2

Liu

Wang

Zhao

et al. 2014

International Journal of Oncology

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Abstract. MicroRNA (miRNA)-126 (miR-126) was reported to be downregulated and to act as a tumor suppressor in cancers of the lung, cervix, bladder and prostate. However, the functions of miR-126 in gastric cancer appear to be diverse and are largely unknown. MiR-126 was reported to act as a tumor suppressor by targeting the Crk gene, or as an oncogene by targeting the SOX2 gene in gastric cancer. We identified that the expression of miR-126 was decreased in gastric cancer cell lines and tissues. PLK2, a tumor suppressor gene, was directly regulated by miR-126 in SGC-7901 cells. Overexpression of miR-126 not only suppressed the growth and clone formation of SGC-7901 cells, but also induced apoptosis in vitro, whereas inhibition of miR-126 slightly promoted SGC-7901 cell proliferation. The cell cycle was not affected by miR-126. Moreover, miR-126 suppressed tumor growth in vivo in a xenograft model. PLK2, PI3KR2and Crk were regulated by miR-126 in SGC-7901 cells. We infer that the functions of miR-126 in gastric cancer depend on synergistic targeting balance between oncogenes and anti-oncogenes. Our study indicates that miR-126 is a tumor suppressor, which in the future may become a therapeutic target for gastric cancer.

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Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells

Cited by 213 publications

References 21 publications

Epidermal Growth Factor–like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

Epidermal Growth Factor–like Domain 7 Predicts Response to First-Line Chemotherapy and Bevacizumab in Patients with Metastatic Colorectal Cancer

miR-126 Is Downregulated in Cystic Fibrosis Airway Epithelial Cells and Regulates TOM1 Expression

miR-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2

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