Dataset Information

Tumour angiogenesis regulation by the miR-200 family.

ABSTRACT: The miR-200 family is well known to inhibit the epithelial-mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Using several experimental models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian, lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization. The role of miR-200 in blocking cancer angiogenesis in a cancer-dependent context defines its utility as a potential therapeutic agent.

SUBMITTER: Pecot CV

PROVIDER: S-EPMC3904438 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumour angiogenesis regulation by the miR-200 family.

Pecot Chad V CV Rupaimoole Rajesha R Yang Da D Akbani Rehan R Ivan Cristina C Lu Chunhua C Wu Sherry S Han Hee-Dong HD Shah Maitri Y MY Rodriguez-Aguayo Cristian C Bottsford-Miller Justin J Liu Yuexin Y Kim Sang Bae SB Unruh Anna A Gonzalez-Villasana Vianey V Huang Li L Zand Behrouz B Moreno-Smith Myrthala M Mangala Lingegowda S LS Taylor Morgan M Dalton Heather J HJ Sehgal Vasudha V Wen Yunfei Y Kang Yu Y Baggerly Keith A KA Lee Ju-Seog JS Ram Prahlad T PT Ravoori Murali K MK Kundra Vikas V Zhang Xinna X Ali-Fehmi Rouba R Gonzalez-Angulo Ana-Maria AM Massion Pierre P PP Calin George A GA Calin George A GA Lopez-Berestein Gabriel G Zhang Wei W Sood Anil K AK

Nature communications 20130101

The miR-200 family is well known to inhibit the epithelial-mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms ...[more]

PMID: 24018975

Similar Datasets

Project description:BackgroundLncRNA-ATB is a long noncoding RNA (lncRNA) activated by transforming growth factor β (TGF-β) and it has important biological functions in tumours and nontumour diseases. Meanwhile, TGF-β is the most critical regulatory factor in the process of nephrotic fibrosis and calcium oxalate (CaOx) crystal-induced renal injury. The present study aimed to investigate the biological function and mechanism of lncRNA-ATB in CaOx crystal-induced renal injury.MethodsThe expression level of lncRNA-ATB was detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), the expression levels of epithelial-mesenchymal transition (EMT) markers, TGF-β1 and Kidney Injury Molecule-1 (KIM-1) were detected by qRT-PCR, immunofluorescence staining or western blot analysis, cell proliferation was measured with a CCK-8 kit, cell apoptosis was measured by flow cytometry and TUNEL staining, and cell injury was detected with the Cytotoxicity lactate dehydrogenase (LDH) Assay kit and the expression level of KIM-1.ResultsThe expression levels of lncRNA-ATB and TGF-β1 were significantly increased in HK-2 cells after coincubation with calcium oxalate monohydrate (COM). COM stimulation caused significant injury in the HK-2 cells, induced cell apoptosis, inhibited cell proliferation, and induced EMT changes. After COM stimulation, the expression levels of the epithelial cell markers E-cadherin and zonula occludens (ZO)-1 in HK-2 cells significantly decreased, whereas the levels of the mesenchymal cell markers N-cadherin, vimentin and α-smooth muscle actin (α-SMA) significantly increased. Interference with lncRNA-ATB expression significantly relieved the COM-induced cell injury, cell apoptosis, proliferation inhibition, and EMT changes. The expression levels of the microRNA-200 (miR-200) family in the HK-2 cells after coincubation with COM were significantly decreased. MiR-200a mimics relieved the COM-induced cell injury, apoptosis, proliferation inhibition, and EMT changes, whereas miR-200a inhibitors abolished the lncRNA-ATB interference-induced relief of the COM-induced cell injury, apoptosis, proliferation inhibition, and EMT.ConclusionLncRNA-ATB promoted the COM-induced cell injury, cell apoptosis, proliferation inhibition, and EMT to participate in the process of CaOx crystal-induced renal injury by sponging miR-200s.

Dataset Information

Tumour angiogenesis regulation by the miR-200 family.

Publications

Tumour angiogenesis regulation by the miR-200 family.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets