Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma.

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Abstract

Definitive radiation therapy is the mainstay of treatment for early stage laryngeal squamous cell carcinoma (LSCC). However, up to 30% of the patients do not respond to radiotherapy. Unfortunately, we are unable to predict which tumors are likely to respond to radiation, and which will be resistant and persist. Therefore, the development of novel markers to predict response to radiotherapy is urgently needed. This study was designed to evaluate the expression pattern of microRNAs (miRNAs) in LSCC in order to identify markers capable of segregating radioresistant and radiosensitive tumors and to investigate the relationship between the expression of these miRNAs and the prognosis of LSCC.

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Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas.

Angela Hui, Melania Pintilie, John Waldron … (2010)

The objective of this study is to investigate the significance of microRNAs (miRNA) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). A global miRNA profiling was done on 51 formalin-fixed archival HNSCC samples using quantitative reverse transcription-PCR approach, correlated with patients' clinical parameters. Functional characterization of HNSCC-associated miRNAs was conducted on three HNSCC cell lines. Cell viability and proliferation were investigated using MTS and clonogenic assays, respectively; cell cycle analyses were assessed using flow cytometry. Thirty-eight of the 117 (33%) consistently detected miRNAs were significantly differentially expressed between malignant versus normal tissues. Concordant with previous reports, overexpression of miR-21, miR-155, let-7i, and miR-142-3p and underexpression of miR-125b and miR-375 were detected. Upregulation of miR-423, miR-106b, miR-20a, and miR-16 as well as downregulation of miR-10a were newly observed. Exogenous overexpression of miR-375 in HNSCC cell lines reduced proliferation and clonogenicity and increased cells in sub-G(1). Similar cellular effects were observed in knockdown studies of the miR-106b-25 cluster but with accumulation of cells in G(1) arrest. No major difference was detected in miRNA profiles among laryngeal, oropharyngeal, or hypopharyngeal cancers. miR-451 was found to be the only significantly overexpressed miRNA by 4.7-fold between nonrelapsed and relapsed patients. We have identified a group of aberrantly expressed miRNAs in HNSCC and showed that underexpression of miR-375 and overexpression of miR-106b-25 cluster might play oncogenic roles in this disease. Further detailed examinations of miRNAs will provide opportunities to dissect the complex molecular abnormalities driving HNSCC progression.

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AngiomiRs--key regulators of angiogenesis.

Shusheng Wang, Eric Olson (2009)

The formation of new blood vessels through the process of angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to a variety of diseases, such as ischemia and cancer. Recent studies have revealed important roles for miRNAs in regulating endothelial cell (EC) function, especially angiogenesis. Mice with EC-specific deletion of Dicer, a key enzyme for generating miRNAs, display defective postnatal angiogenesis. Specific miRNAs (angiomiRs) have recently been shown to regulate angiogenesis in vivo. miRNA-126, an EC-restricted miRNA, regulates vascular integrity and developmental angiogenesis. miR-378, miR-296, and the miR-17-92 cluster contribute to tumor angiogenesis. Manipulating angiomiRs in the settings of pathological vascularization represents a new therapeutic approach.

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miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells.

Thomas Würdinger, Bakhos A Tannous, Okay Saydam … (2008)

A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells. Here, we demonstrate that a small regulatory microRNA, miR-296, has a major role in this process. Glioma cells and angiogenic growth factors elevate the level of miR-296 in primary human brain microvascular endothelial cells in culture. The miR-296 level is also elevated in primary tumor endothelial cells isolated from human brain tumors compared to normal brain endothelial cells. Growth factor-induced miR-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor receptors VEGFR2 and PDGFRbeta. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo.

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Author and article information

Journal

Journal ID (iso-abbrev): J Transl Med

Title: Journal of translational medicine

Publisher: Springer Nature

ISSN (Electronic): 1479-5876

ISSN (Print): 1479-5876

Publication date (Electronic): Aug 12 2015

Volume: 13

Affiliations

[1 ] Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of São Paulo, Rua Pedro de Toledo, 669-11° andar, São Paulo, SP, 04039-032, Brazil. dellymaia@gmail.com.

[2 ] Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of São Paulo, Rua Pedro de Toledo, 669-11° andar, São Paulo, SP, 04039-032, Brazil. ca_oak@yahoo.com.br.

[3 ] Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP, 14784-400, Brazil. ca_oak@yahoo.com.br.

[4 ] Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of São Paulo, Rua Pedro de Toledo, 669-11° andar, São Paulo, SP, 04039-032, Brazil. aderuza@gmail.com.

[5 ] Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP, 14784-400, Brazil. alopescarvalho@uol.com.br.

[6 ] Department of Head and Neck Surgery, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, 14784-400, Brazil. alopescarvalho@uol.com.br.

[7 ] Department of Pathology, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, Barretos, 14784-400, Brazil. cristovamscapula@uol.com.br.

[8 ] Laboratory of Molecular Cancer Biology, Department of Biological Sciences, Federal University of São Paulo, Rua Pedro de Toledo, 669-11° andar, São Paulo, SP, 04039-032, Brazil. andre.vettore@gmail.com.

[9 ] Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore. andre.vettore@gmail.com.

Article

Publisher Item ID: 10.1186/s12967-015-0621-y

DOI: 10.1186/s12967-015-0621-y

PMC ID: 4533949

PubMed ID: 26264462

SO-VID: 8f932143-a672-4690-a8e4-e91cca6a7ffc

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Expression of miR-296-5p as predictive marker for radiotherapy resistance in early-stage laryngeal carcinoma.

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New directions in predictive processing

Most cited references 34

Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas.

AngiomiRs--key regulators of angiogenesis.

miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells.

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