JCI early table of contents for Feb. 15, 2013

February 15, 2013

A smoking gun in lung cancer epigenetics

Recent studies have identified correlations between cigarette smoke-induced microRNA (miRNA) expression and different aspects of lung cancer; however, it is unclear how miRNA expression directly contributes to carcinogenesis. MiRNAs regulate the expression of target genes and can have a significant impact on when and how well different gene products are expressed. In this issue of the Journal of Clinical Investigation, David Schrump and colleagues at the National Cancer Institute in Bethesda, MD, measured miRNA expression in normal human lung cells exposed to cigarette smoke condensate (CSC) and lung cancer cells derived from smokers and non-smokers. They found that CSC exposure repressed the miRNA-487b. Loss of miRNA-487b increased the expression of five critical oncogenes and enhanced the proliferation, invasion, tumorigenicity, and metastatic capacity of lung cells. Loss of miRNA-487b and concomitant up-regulation of the five oncogenes was also observed in patient lung cancer specimens. These results reveal a direct mechanism by which cigarette smoke-induced miRNA alterations promote lung carcinogenesis.

TITLE:
Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis

AUTHOR CONTACT:
David Schrump
National Cancer Institute, Bethesda, MD, USA
Phone: 301-496-2128; E-mail: david_schrump@nih.gov

View this article at: http://www.jci.org/articles/view/61271?key=1f628155b6680108ff1a


Researchers identify a factor that may contribute to increased heart attack-related mortality in diabetics

Diabetic patients are more than twice as likely to die from a heart attack as non-diabetic patients, but the mechanisms that underlie increased heart attack-related mortality in diabetic patients are unknown. High levels of the oxidized form of the protein CamKII (ox-CaMKII) have been linked to increased risk of sudden death after heart attack. Additionally, hearts from diabetic patients have significantly greater ox-CAMKII compared to hearts from non-diabetic patients. In this issue of the Journal of Clinical Investigation, Min Luo and colleagues at the University of Iowa used a mouse model of diabetest to determine if ox-CAMKII was an essential component of the molecular pathway that increases heart attack-related mortality in diabetic patients. The transgenic mouse model was engineered to express a form of CaMKII that cannot be oxidized in the heart muscle. Luo and colleagues found that diabetic mice expressed the non-oxidizable form of CamKII were less likely to die after a heart attack than mice that expressed normal CamKII. These findings suggest that ox-CAMKII may also increase post-heart attack mortality in diabetic patients and indicate that therapies that reduce oxidation of CamKII could be useful in treating diabetic patients who suffer from cardiovascular disease.

TITLE:
Diabetes increases mortality after myocardial infarction by oxidizing CaMKII

AUTHOR CONTACT:
Min Luo
University of Iowa Hospitals & Clinics, Iowa city, IA, USA
Phone: 319-356-2745; Fax: 319-356-8608; E-mail: min-luo-1@uiowa.edu

View this article at: http://www.jci.org/articles/view/65268?key=092be585f593debb00e1

ALSO IN THIS ISSUETITLE:
Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis

AUTHOR CONTACT:
Goran Hansson
Karolinska Institutet, Stockholm, SWE
Phone: 08-517-762-22; Fax: 46-8-313147; E-mail: Goran.Hansson@ki.se

View this article at: http://www.jci.org/articles/view/63891?key=c1df843db2cf77228eea

TITLE:
Mitochondrial Complex I activity and NAD+/NADH balance regulate breast cancer progression

AUTHOR CONTACT:
Brunhilde Felding-Haberman
Scripps Research Institute, La Jolla, CA, USA
Phone: 858-784-2021; E-mail: brunie@scripps.edu

View this article at: http://www.jci.org/articles/view/64264?key=790b11e14555fb86bf85

TITLE:
IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality

AUTHOR CONTACT:
Hana Algul
Technical University of Munich, Munich, DEU
Phone: 49-89-41406792; E-mail: hana.alguel@lrz.tum.de

View this article at: http://www.jci.org/articles/view/64931?key=5cdcf8375cd08827aa82

TITLE:
Hypoxia-responsive miRNAs target argonaute 1 to promote angiogenesis

AUTHOR CONTACT:
John Y-J. Shyy
University of California, Riverside, Riverside, CA, USA
Phone: 951-827-3863; Fax: 951-827-5504; E-mail: john.shyy@ucr.edu

View this article at: http://www.jci.org/articles/view/65344?key=5fab53e050196df9d18b

TITLE:
ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer

AUTHOR CONTACT:
Steven Balk
Beth Israel Deaconess Medical Center, Boston, MA, USA
Phone: 617-735-2065; Fax: 617-735-2050; E-mail: sbalk@bidmc.harvard.edu

View this article at: http://www.jci.org/articles/view/66666?key=ebfd1fb6b15a5fd9a7ea
-end-


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