The many complex roles of microRNA in breast cancer

by Chris on February 10, 2010

in Technical Article

There have been several studies involving microRNAs and breast cancer to date.  The findings of these studies collectively demonstrate the wide range of function that microRNA can play in just a single disease.  Researchers at Baylor College of Medicine and the University of Houston found that dysregulation of certain microRNAs have significant effect on morphological and molecular changes such as an expansion of the progenitor cell population, decreased cell size, increased cellular proliferation, and colony-forming potential [1]. They suggest that the dysregulation of these microRNAs might be important in the causation, or origination of breast cancer.

Cancer cells that develop resistance to chemotherapeutic agents are a major clinical obstacle in the successful treatment of breast cancer.  Researchers at the University of Lethbridge, Canada found that chemoresistance may be linked to drug-induced dysregulation of microRNA function [2]. They found many dysregulated microRNAs in drug resistant MFC-7 human breast adenocarcinoma cells and that some of these microRNAs target a human multidrug resistance-associated protein. Their results suggest that dysregulated microRNA expression may underlie the abnormal functioning of critical cellular processes associated with the chemoresistance phenotype.

A major complication of breast cancer is its metastatic potential and now, some new studies have shown that microRNAs can affect breast cancer metastasis either by over or under expression.  In this first example, researchers show that over expression of a specific microRNA plays a key role in a cancer signaling pathway. It is known that Rho-associated kinase (ROCK) signaling plays a fundamental role in regulating cell morphology, adhesion, and motility and that aberrant expression of ROCK is related to tumor metastases and poor clinical outcome. Researchers at Tufts University found that addition of an anti-miR can block the ROCK signaling pathway resulting in decreased breast cancer cell invasion/ migration and metastasis [3].

In another study, it was found that microRNAs function in an opposite manner. Researchers at Memorial Sloan-Kettering Cancer Center found a specific set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential [8]. Furthermore, they show that restoring the expression of these microRNAs in malignant cells reduces overall tumor growth and proliferation and suppresses metastatic cell invasion.

  1. Greene SB, Gunaratne PH, Hammond SM, Rosen JM. (2010) A putative role for microRNA-205 in mammary epithelial cell progenitors. J Cell Sci [Epub ahead of print] [abstract]
  2. Pogribny IP, Filkowski JN, Tryndyak VP, Golubov A, Shpyleva SI, Kovalchuk O. (2010) Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int J Cancer [Epub ahead of print] [abstract]
  3. Liu S, Goldstein RH, Scepansky EM, Rosenblatt M.  (2009) Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone.  Cancer Res 69(22), 8742-751.   [abstract]
  4. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J.  (2009) miR-200 enhances mouse breast cancer cell colonization to form distant metastasesPLoS One 4(9), e7181.  [abstract]
  5. Wickramasinghe NS, Manavalan TT, Dougherty SM, Riggs KA, Li Y, Klinge CM. (2009) Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells. Nucleic Acids 37(8), 2584-95.  [abstract]
  6. Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y, Joshua Liao D. (2008) Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat 118(1), 185-96.  [abstract]
  7. 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]
  8. Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451(7175), 147-52.  [abstract]
  9. Kovalchuk O, Tryndyak VP, Montgomery B, Boyko A, Kutanzi K, Zemp F, Warbritton AR, Latendresse JR, Kovalchuk I, Beland FA, Pogribny IP. (2007) Estrogen-induced rat breast carcinogenesis is characterized by alterations in DNA methylation, histone modifications and aberrant microRNA expression. Cell Cycle 6(16), 2010-18.  [abstract]

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