microRNA of the Week: microRNA-451

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]