Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma

Childs, Geoffrey; Fazzari, Melissa; Kung, Gloria; Kawachi, Nicole; Brandwein-Gensler, Margaret; McLemore, Michael Steven; Chen, Quan; Burk, Robert D.; Smith, Richard V.; Prystowsky, Michael B.; Belbin, Thomas J.; Schlecht, Nicolas F.

doi:10.2353/ajpath.2009.080731

Cited by 327 publications

(297 citation statements)

References 41 publications

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“…ARF4 interacts with EGFR, thereby enhancing oncogenic processes. 47 On the other hand, the loss of hsa-miR-205 shown in malignant prostate tissue in our study (Table 2) and by others 11 as well as in other cancer types 48,49 is suggested a hallmark of epithelial-mesenchymal transition. Hsa-miR-205 targets SIP1 and ZEP which promote this transition.…”

Section: Discussionmentioning

confidence: 57%

Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma

Schaefer

Jung

Mollenkopf

et al. 2009

Intl Journal of Cancer

561

491

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This study aimed to investigate the microRNA (miRNA) profile in prostate carcinoma tissue by microarray analysis and RT-qPCR, to clarify associations of miRNA expression with clinicopathologic data and to evaluate the potential of miRNAs as diagnostic and prognostic markers. Matched tumor and adjacent normal tissues were obtained from 76 radical prostatectomy specimens. Twenty-four tissue pairs were analyzed using human miRNA microarrays for 470 human miRNAs. Differentially expressed miRNAs were validated by TaqMan RT-qPCR using all 76 tissue pairs. The diagnostic potential of miRNAs was calculated by receiver operating characteristics analyses. The prognostic value was assessed in terms of biochemical recurrence using Kaplan-Meier and Cox regression analyses. Fifteen differentially expressed miRNAs were identified with concordant fold-changes by microarray and RT-qPCR analyses. Ten microRNAs (hsa-miR-16, hsa-miR-31, hsa-miR-125b, hsamiR-145, hsa-miR-149, hsa-miR-181b, hsa-miR-184, hsa-miR-205, hsa-miR-221, hsa-miR-222) were downregulated and 5 miRNAs (hsa-miR-96, hsa-miR-182, hsa-miR-182*, hsa-miR-183, hsa-375) were upregulated. Expression of 5 miRNAs correlated with Gleason score or pathological tumor stage. Already 2 microRNAs classified up to 84% of malignant and nonmalignant samples correctly. Expression of hsa-miR-96 was associated with cancer recurrence after radical prostatectomy and that prognostic information was confirmed by an independent tumor sample set from 79 patients. That was shown with hsa-miR-96 and the Gleason score as final variables in the Cox models build in the 2 patient sets investigated. Thus, differential miRNAs in prostate cancer are useful diagnostic and prognostic indicators. This study provides a solid basis for further functional analyses of miRNAs in prostate cancer.

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Section: Discussionmentioning

confidence: 57%

Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma

Schaefer

Jung

Mollenkopf

et al. 2009

Intl Journal of Cancer

561

491

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“…We found that hsamiR-21 was higher in tumor than normal tissue, in keeping with previous studies showing its overexpression in HNSCC. 23 hsa-miR-10b expression was lower in tumor than normal tissue, again in keeping with our previous result in breast cancer, 32 and that of Childs et al in HNSCC, 33 but conflicting with the finding of Ma et al 18 Given our previous finding that the adjacent normal tissue had a lower hypoxia score by metagene than its matched tumor, 7 we were expecting that hsa-miR-210 would be lower in normal than in tumor tissue. However, for hsamiR-210, expression in some tumors was higher than matched normal tissue, and expression in others was lower.…”

Section: Discussionmentioning

confidence: 58%

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Gee

Camps

Buffa

et al. 2010

Cancer

224

157

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BACKGROUND:Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis. METHODS: Three hypoxia-related microRNAs, hsa-miR-210, hsa-miR-21, and hsa-miR-10b, were measured in 46 samples from patients with HNSCC. Expression levels were correlated with clinicopathological variables and other markers of hypoxia: a published 99-gene hypoxia metagene, individual hypoxia-related genes such as TWIST1, and immunohistochemical expression of hypoxia-inducible factor 1 and its target gene carbonic anhydrase 9. We then performed survival analyses to investigate the prognostic significance of these microRNAs. RESULTS: Only the level of hsa-miR-210 was significantly correlated with other markers of hypoxia, including the 99-gene hypoxia metagene (rho ¼ 0.67, P < .001). We found no association between hsa-miR-210, hsamiR-21, or hsa-miR-10b and clinicopathological variables such as tumor size, differentiation, and stage. However, high levels of hsa-miR-210 were associated with locoregional disease recurrence (P ¼ .001) and short overall survival (P ¼ .008). hsa-miR-21 and hsa-miR-10b had no prognostic significance. CONCLUSIONS: Expression of hsa-miR-210 in head and neck cancer correlates with other approaches for assessing hypoxia and is associated with prognosis. This warrants further study as a classification marker of patients for therapies involving modulation of hypoxia.

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“…MiR-205 might also regulate EMT by targeting ZEB1 and SIP1 in collaboration with miR-200 family miRNA including miR-200c (16,18) and target the HER3 oncogene in human breast cancer. (45) It has recently been reported that low-level expression of miR-205 is a prognostic marker of HNSCC, (46) and that downregulation of microRNA of the miR-200 family and miR-205 and an altered expression of classic and desmosomal cadherins were observed in spindle cell carcinoma of the head and neck with EMT. (47) Therefore, in addition to miR-200c, downregulation of miR-205 after HGF stimulation might also play an important role in progression of HNSCC with EMT.…”

Section: Discussionmentioning

confidence: 99%

Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma

et al. 2011

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Hepatocyte growth factor (HGF) is a multifunctional molecule that acts as mitogen, motogen, and ⁄ or morphogen in a variety of cells. MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including squamous cell carcinoma of the human head and neck (HNSCC), but how HGF affects the expression of downstream functional genes has not yet been elucidated in detail. In the present study, we examined the expression of micro-RNA (miRNA), non-coding small RNA that regulate cell proliferation and functions by interfering with the translation of target mRNA, with or without HGF stimulation in HNSCC cell line HSC3. Among several miRNAs, in which the expression was altered after HGF stimulation, we focused on miR-200c and miR-27b, both of which were drastically downregulated after HGF stimulation. Expression of ZEB1, a target mRNA for miR-200c, was upregulated 3 and 6 h after HGF stimulation, and that of E-cadherin, a downstream molecule of ZEB1, was downregulated 12 h after HGF stimulation. Expression of ST14 ⁄ matriptase, an enzyme for extracellular matrix (ECM) degradation and HGF activation and a target mRNA for miR-27b, was drastically upregulated in the protein level after HGF stimulation, although it was not statistically altered in the mRNA level. These results suggest that miR-200c and miR-27b downregulated by HGF might play an important role in epithelialmesenchymal transition mediated by ZEB1 ⁄ E-cadherin and ECM degradation and HGF autoactivation mediated by ST14 ⁄ matriptase, respectively. Altered expression of miRNA directly regulated by HGF might contribute enhanced progressive and invasive characteristics of HNSCC by regulating the translation of HGF-induced functional molecules. (Cancer Sci 2011; 102: 2164-2171 S quamous cell carcinoma (SCC) is a common malignant tumor in the head and neck and constitutes 90% of malignancies in these regions.(1,2) The incidence and mortality of head and neck SCC (HNSCC) is increasing despite intense efforts, and its 5-year survival rate is <50%.(2,3) Several growth factors are considered to contribute to the carcinogenesis and progression of HNSCC.(2) One of these factors, hepatocyte growth factor (HGF), is a multifunctional growth factor that acts as mitogen, motogen and ⁄ or morphogen in a variety of cells including squamous epithelial cells.(4-6) MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including human HNSCC, and its signal transduction to the nucleus induces the expression of genes involving the progressive and invasive characteristics of HNSCC.(5-7) However, how HGF affects downstream functional gene expression has not yet been elucidated in detail.MicroRNA (miRNA) are non-coding small RNA (21-25 nucleotides) that regulate post-transcriptional gene expression by interfering with the translation of target mRNA. (8,9) One miRNA might regulate the expression of several genes and over one-third of all protein-coding genes might be under translational control by miRNA. (9) MiRNA are involved in a variety ...

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Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma

Cited by 327 publications

References 41 publications

Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma

Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma

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