head and neck cancer

Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas.

Researchers at Department of Pathology, Albert Einstein College of Medicine used global miRNA expression profiling of head and neck squamous cell carcinoma (HNSCC) samples and adjacent normal tissue to rank those miRNAs that were most significantly altered in a patient population of 123. Harris et al. evaluated 736 of the currently known 1898 unique mature human microRNAs. Rank Consistency Score analysis revealed miR-375 to have the most significantly lowered miRNA levels in tumors relative to matched adjacent nonmalignant tissue from the same patient.

While this result has been previously observed by other groups, this latest study reveals that low miR-375 expression levels correlate significantly with cancer survival and distant metastasis. In a study of 123 primary HNSCC patients using multivariable Cox proportional hazard ratios (HR) and 95% confidence intervals (CI), both death from disease (HR: 12.8, 95% CI: 3 to 49) and incidence of distant metastasis (HR: 8.7, 95% CI: 2 to 31) correlated with lower expression levels of miR-375 regardless of the site or stage of the tumor. In addition, oral cavity tumor cell lines (eg, UMSCC1 and UMSCC47) overexpressing miR-375 were significantly less invasive in vitro than their matched empty vector controls.

The authors conclude that miR-375 may be suitable as a potential prognostic marker of poor outcome and metastasis in HNSCC and that it may function by suppressing the tumor’s invasive properties.

Harris T, Jimenez L, Kawachi N, Fan JB, Chen J, Belbin T, Ramnauth A, Loudig O, Keller CE, Smith R, Prystowsky MB, Schlecht NF, Segall JE, Childs G.
Low-Level Expression of miR-375 Correlates with Poor Outcome and Metastasis While Altering the Invasive Properties of Head and Neck Squamous Cell Carcinomas.
Am J Pathol., in press.



microRNA of the Week: microRNA-451

by Chris on February 26, 2010

in Technical Article

Hypoxia and monocrotaline induced strong upregulation of miR-451 suggesting a role in the development of pulmonary arterial hypertension (PAH)1, a complex disorder leading to right-sided heart failure and death. Head and neck squamous cell carcinomas (HNSCC) constitute the fifth most common malignancy worldwide. Significant downregulation of miR-451 was observed in relapsed HNSCC patients suggesting that downregulation of miR-451 could be a viable candidate marker for HNSCC2. Underexpression of miR-451 has been associated with worse prognosis in gastric cancer, with macrophage inhibitor factor suggested as its potential mRNA target3. Increasing Evidence has suggested that bronchioalveolar stem cell (BASC) is the progenitor cells of lung cancer stem cells. It has been shown that BASCs possess a unique miRNA profile, with altered expression of several microRNAs, such as miR-451 in BASCs compared to control cells. These results suggest that microRNAs might play important roles in maintaining the self-renewal capacity of BASCs, and that aberrant expression of microRNAs could be involved in turning BASCs into lung cancer stem cells4. Finally, miR-451 seems to be a key molecule in normal erythroid differentiation and has also been shown to regulate the multidrug resistance 1 gene in cervix, ovarian, and breast cancer cell lines5.

  1. Caruso P, Maclean MR, Khanin R, McClure J, Soon E, Southwood M, McDonald RA, Greig JA, Robertson KE, Masson R, Denby L, Dempsie Y, Long L, Morrell NW, Baker AH. (2010) Dynamic Changes in Lung MicroRNA Profiles During the Development of Pulmonary Hypertension Due to Chronic Hypoxia and Monocrotaline. Arterioscler Thromb Vasc Biol [Epub ahead of print] [abstract]
  2. Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, Perez-Ordonez B, Jurisica I, O’Sullivan B, Waldron J, Gullane P, Cummings B, Liu FF. (2010) Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 16(4):1129-39. [abstract]
  3. Bandres E, Bitarte N, Arias F, et al. (2009) microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 15:2281–90. [abstract]
  4. Qian S, Ding JY, Xie R, An JH, Ao XJ, Zhao ZG, Sun JG, Duan YZ, Chen ZT, Zhu B. (2008) MicroRNA expression profile of bronchioalveolar stem cells from mouse lung. Biochem Biophys Res Commun 377(2), 668-73. [abstract]
  5. Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF, Pogribny IP. (2008) Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther 7(7), 2152-59. [abstract]

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MicroRNA Profiling and Head and Neck Cancer

by Chris on September 25, 2009

in Publications

miRNA profiling and head and neck cancerRecent advances in microRNA expression profiling have led to a better understanding of the HNOC pathogenesis. This will lead to the identification of specific microRNA expression patterns that may become powerful biomarkers for diagnosis and prognosis of HNOC. In addition, these microRNAs may also serve as therapeutic targets for novel strategies of HNOC prevention and therapeutics. Read the full review article here:

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