Epigenetic silencing of miR-145-5p contributes to brain metastasis

被引：72

作者：

Donzelli, Sara ^{[1
]}

Mori, Federica ^{[2
]}

Bellissimo, Teresa ^{[1
]}

Sacconi, Andrea ^{[1
]}

Casini, Beatrice ^{[3
]}

Frixa, Tania ^{[1
]}

Roscilli, Giuseppe ^{[4
]}

Aurisicchio, Luigi ^{[4
]}

Facciolo, Francesco ^{[5
]}

Pompili, Alfredo ^{[6
]}

Carosi, Maria Antonia ^{[3
]}

Pescarmona, Edoardo ^{[3
]}

Segatto, Oreste ^{[7
]}

Pond, Greg ^{[8
]}

Muti, Paola ^{[8
]}

Telera, Stefano ^{[6
]}

Strano, Sabrina ^{[2
,8
]}

Yarden, Yosef ^{[9
]}

Blandino, Giovanni ^{[1
,8
]}

机构：

[1] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy

[2] Italian Natl Canc Inst Regina Elena, Mol Chemoprevent Unit, Rome, Italy

[3] Italian Natl Canc Inst Regina Elena, Dept Pathol, Rome, Italy

[4] Takis Srl, Rome, Italy

[5] Italian Natl Canc Inst Regina Elena, Unit Thorac Surg, Rome, Italy

[6] Italian Natl Canc Inst Regina Elena, Dept Neurosurg, Rome, Italy

[7] Italian Natl Canc Inst Regina Elena, Lab Cell Signaling, Rome, Italy

[8] McMaster Univ, Fac Hlth Sci, Dept Oncol, Hamilton, ON, Canada

[9] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

来源：

ONCOTARGET | 2015年 / 6卷 / 34期

关键词：

brain metastases; lung cancer; mir-145-5p; epigenetic modifications; migration; CANCER-CELL-MIGRATION; HUMAN BREAST-TUMORS; LUNG ADENOCARCINOMA; MICRORNA; INVASION; EXPRESSION; PROLIFERATION; SUPPRESSES; CARCINOMA; MELANOMA;

D O I：

10.18632/oncotarget.5930

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.

引用

页码：35183 / 35201

页数：19

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