In Nature this week, researchers from California and Maryland report their findings that the translational landscape of mTOR signaling has an influence on cancer initiation and metastasis. The team used ribosome profiling to find specialized translation of the prostate cancer genome by oncogenic mTOR signaling, suggesting that there is a specific group of genes involved in cell proliferation, metabolism, and invasion. "We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signaling," the authors write. They further developed a clinically relevant ATP site inhibitor of mTOR, INK128, which works by reprogramming the gene expression signature to prevent prostate cancer metastasis.
Also in Nature this week, researchers in Florida and Texas report their use of synthetic REV-ERB agonists to regulate circadian behavior and metabolism. The researchers found that synthetic REV-ERB ligands can alter circadian behavior and the circadian pattern of core clock gene expression in the hypothalami of mice. Further, the team says the synthetic ligands also altered the circadian pattern of various metabolic genes in the liver, skeletal muscle, and adipose tissue, which resulted in an increased expenditure of energy. "Treatment of diet-induced obese mice with a REV-ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidemia and hyperglycemia," the authors write. "These results indicate that synthetic REV-ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases."
In Nature Genetics this week, an international team of researchers reports its genome-wide meta-analysis of bone-mineral density loci. The team analyzed data from 17 genome-wide association studies and 32,961 individuals, and identified 56 loci associated with bone mineral density at genome-wide significance and a further 14 loci associated with risk of fracture. "These findings shed light on the genetic architecture and pathophysiological mechanisms underlying bone mineral density variation and fracture susceptibility," the authors write.
Finally, in Nature Medicine this week, researchers in New York and China describe the approach they took to identify HIPK2 as a key regulator of kidney fibrosis. Using an integrated computational and experimental systems biology approach, the team found protein kinases that regulate gene expression changes in the kidneys of HIV-transgenic mice. "We identified homeo-domain interacting protein kinase 2 as a key regulator of kidney fibrosis," they write. "HIPK2 was upregulated in the kidneys of Tg26 mice and in those of patients with various kidney diseases. HIV infection increased the protein concentrations of HIPK2 by promoting oxidative stress."