mir-143

miR-143/145 show promise against pancreatic cancer

by Chris on December 17, 2010

Missing Molecules Hold Promise of Therapy for Pancreatic Cancer

From Johns Hopkins

By determining what goes missing in human cells when the gene that is most commonly mutated in pancreatic cancer gets turned on, Johns Hopkins scientists have discovered a potential strategy for therapy.

The production of a particular cluster of genetic snippets known as microRNAs is dramatically reduced in human pancreatic tumor cells compared to healthy tissue, the researchers report in a study published Dec. 15 in Genes and Development. When the team restored this tiny regulator, called miR-143/145, back to normal levels in human pancreatic cancer cells, those cells lost their ability to form tumors.

“Our finding that these specific microRNAs are downstream of the most important oncogene in pancreatic cancer sets the stage for developing methods to deliver them to tumors,” says Josh Mendell, M.D., Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, and an early career scientist of the Howard Hughes Medical Institute.  “When we restore microRNAs to cancer cells in which their levels are repressed, the cells no longer are tumorigenic. We have every reason to believe that the efficient delivery of miR-143/145, if achievable, would be therapeutically beneficial.”

(read the entire release… )

Kent OA, Chivukula RR, Mullendore M, Wentzel EA, Feldmann G, Lee KH, Liu S, Leach SD, Maitra A, Mendell JT. (2010) Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev 24(24), 2754-59. [abstract]

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MicroRNAs control injury response in smooth muscle cells

by Chris on November 24, 2009

Researchers at the University of Texas Southwestern Medical Center, Dallas used microarray analysis to compare miRNA expression patterns of primary rat cardiomyocytes with different levels of myocardin-related transcription factors (MRTFs). MRTFs associate with serum response factor (SRF) to drive the expression of actin and other cytoskeletal protein genes. miR-145 and miR-143 were among the most strongly upregulated miRNAs in response to MRTFs, as revealed by microarray and confirmed by real-time PCR. Further study revealed that (SRF) controls the expression of miR-143 and miR-145 in smooth muscle cells, and these miRNAs, in turn, feed back to control the expression and function of multiple components of the cytoskeleton and the SRF regulatory network. This study adds to a growing body of work demonstrating the roles of miRNAs in regulating changes in gene expression and cell functions in response to injury and stress and further underscores their potential as therapeutic targets.

Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R, Olson EN.  (2009) MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury.  Genes Dev 23(18),2166-178. [abstract]

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