Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor

Zehavi, Liron; Avraham, Roi; Barzilai, Aviv; Bar-Ilan, Dalia; Navon, Roy; Sidi, Yechezkel; Avni, Dror; Leibowitz-Amit, Raya

doi:10.1186/1476-4598-11-44

Cited by 126 publications

(119 citation statements)

References 49 publications

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“…org), indicated that insulin-like growth factor 1 receptor (IGF1-R) and vascular endothelial zinc finger-1 (VEZF1) are theoretically the targets of miR-376a. VEGF has been demonstrated to be induced by IGF1-R and IGF1-R is a target of miR-376a (Warren et al, 1996;Zehavi et al, 2012). At the same time, VEZF1 also has the ability to enhance the expression of VEGF in tumor angiogenesis (Bruderer et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNA-376a (miR-376a) has been reported in several human cancers, including upregulation in esophageal cancer tissues, plasma of breast cancer, and downregulation in melanoma, and hepatocellular carcinoma (Zehavi et al, 2012;Zheng et al, 2012;Cuk et al, 2013;Zhao et al, 2013). In particular, Kunte et al found that levels of miR-376a expression were significantly increased with CRC tumor development, using the azoxymethane (AOM)-treated rat model (Kunte et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Wu²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptasepolymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical followup information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Wu²,

Li³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…5 And miR-7-5p partially inhibits IRS-2 expression and Akt signaling pathway. 6 Conversely,miR-195 can be targeted to regulate WEE1, 7 miR-182regulates MATF-M and FOXO3, 8 miR-193b can down-regulate STMN1 expression, and miR-376a and miR-376c control the expression of IGF1R, 9 in order to promote proliferation, invasion and metastasis of melanoma. 10 Up to now, the special molecular mechanism by which microRNA in melanoma affects the tumor invasion and metastasis is still unclear.…”

Section: Introductionmentioning

confidence: 99%

miR-33a functions as a tumor suppressor in melanoma by targeting HIF-1α

Zhou¹,

Xie

et al. 2015

Cancer Biology & Therapy

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Abbreviations: miR-33a/b, microRNA 33a/b; HIF-1a, hypoxia inducible factor 1, a subunit Background: Our previous findings showed that miR-33 expressed abnormally in clinical specimens of melanoma, but the exact molecular mechanism has not been elucidated. Object: To determine miR-33's roles in melanoma and confirm whether HIF-1a is a direct target gene of miR-33a. Methods: First miR-33a/b expression levels were detected in HM, WM35, WM451, A375 and SK-MEL-1. Then lentiviral vectors were constructed to intervene miR-33a expression in melanoma cells. Cell proliferation, invasion and metastasis were detected. A375 cells mice model was performed to test the tumorigenesis of melanoma in vivo. Finally the dual reporter gene assay was carried out to confirm whether HIF-1a is a direct target gene of miR-33a. Results: MiR-33a/b exhibited a lower expression in WM35, WM451, A375 and SK-MEL-1 of the metastatic skin melanoma cell lines than that in HM. Then inhibition of miR-33a expression in WM35 and WM451 cell lines could promote cell proliferation, invasion and metastasis. Conversely, increased expression of miR-33a in A375 cells could inhibit cellproliferation, invasion and metastasis. In vivo tests also confirmed that overexpression of miR-33a in A375 cells significantly inhibited melanoma tumorigenesis. Finally, we confirmed that HIF-1a is a direct target gene of miR-33a. Conclusion: The newly identified miR-33a/HIF-1a axis might provide a new strategy for the treatment of melanoma.

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“…Bioinformatic analysis of these miRNAs predicted binding sites in the 3 0 -UTR of IGF1R. In the cell lines overexpressing mir-376a and c, IGF1R mRNA and protein levels were decreased (Zehavi et al 2012). There is evidence of reduced IGF1 signalling in Mirg knock-out mice, because they have reduced hepatic Igf1 mRNA, and have shown transient growth restriction around the time of weaning (Labialle et al 2014).…”

Section: Dlk1mentioning

confidence: 97%

Molecular basis of imprinting disorders affecting chromosome 14: lessons from murine models

Howard

Charalambous

2015

Reproduction

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Uniparental inheritance of chromosome 14q32 causes developmental failure during gestation and early postnatal development due to mis-expression of a cluster of imprinted genes under common epigenetic control. Two syndromes associated with chromosome 14q32 abnormalities have been described, Kagami-Ogata and Temple syndromes. Both of these syndromes are characterised by specific impairments of intrauterine development, placentation and early postnatal survival. Such abnormalities arise because the processes of intrauterine growth and postnatal adaptation are critically modulated by the dosage of imprinted genes in the chromosome 14q32 cluster. Much of our understanding of how the imprinted genes in this cluster are regulated, as well as their individual functions in the molecular pathways controlling growth and postnatal adaptation, has come from murine models. Mouse chromosome 12qF1 contains an imprinted region syntenic to human chromosome 14q32, collectively referred to as the Dlk1-Dio3 cluster. In this review, we will summarise the wealth of information derived from animal models of chromosome 12 imprinted gene mis-regulation, and explore the relationship between the functions of individual genes and the phenotypic result of their mis-expression. As there is often a considerable overlap between the functions of genes in the Dlk1-Dio3 cluster, we propose that the expression dosage of these genes is controlled by common regulatory mechanisms to co-ordinate the timing of growth and postnatal adaptation. While the diseases associated with mis-regulated chromosome 14 imprinting are rare, studies carried out in mice on the functions of the affected genes as well as their normal regulatory mechanisms have revealed new mechanistic pathways for the control of growth and survival in early life.Reproduction (2015) 149 R237-R249

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Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor

Cited by 126 publications

References 49 publications

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

miR-33a functions as a tumor suppressor in melanoma by targeting HIF-1α

Molecular basis of imprinting disorders affecting chromosome 14: lessons from murine models

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