stem cells

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 Increases Understanding of Molecular Circuitry

by Chris on June 9, 2009

in Publications

The mechanism of regulation by microRNA (miRNA) is complex in that miRNAs are frequently transcribed together as primary transcripts that are then processed into multiple individual mature miRNAs and, that each individual miRNA may target many different mRNAs.  Thus miRNA represents a network of control over cellular functions.  Additionally, the organization of many clusters of miRNAs is highly conserved and this suggests an important role for coordinated programmable function.  Expression profiling of complete “microRNA-omes” enables researchers to look at this network on a broad scale and better understand the interrelationship of factors at work.

It has now been well established that miRNAs are important for the regulation of many cellular activities including cell development and differentiation.  MicroRNAs play particularly important roles in human embryonic stem cells (hESC), possibly regulating self-renewal, pluripotency and differentiation.  Furthermore, a better understanding of the molecular circuitry involved with reprogramming of adult cells into induced pluripotent stem cells (iPSCs) could lead to better methods of which would circumvent the need to use human embryos for research and possibly lead to the creation of disease-specific stem cells as model systems. [click to continue…]

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