Retroviruses have helped shape the evolution of gene regulation, as highlighted by the mouse VL30-1 RNA that probably arose from a retrovirus infection. In a review article, Alan Garen from Yale University discusses the regulatory properties of VL30-1 RNA that control the expression of multiple genes, including those involved in cell proliferation and cancer. VL30-1 forms a complex with a tumor-suppressor protein called PSF that keeps tumor growth in check, inactivating PSF and promoting cell proliferation and cancer. VL30-1 RNA may have derived from a harmful genomic invader, but over evolutionary time it has co-opted the function of an endogenous regulatory RNA and become indispensable for normal mouse development and survival. Other RNAs that have a similar regulatory function as VL30-1 RNA exist in human cell.
Chemical agents that bind and reversibly modifyspecific DNA sequences could provide the foundation for safer anticancertreatments. Seeing that many current chemotherapy agents kill cancer cells byintroducing irreversible modifications at any site in the genome—damagingnon-target cells while also depleting the amount of drug available to fightcancer—Steven Rokita at the University of Maryland, along with colleagues inChina, sought a more selective and safer approach to treatment. They combinedDNA-modifying compounds known as quinone methides with nucleic acid constructsthat specifically bind particular gene sequences, allowing for targetedtreatment. Importantly, these chemical modifications are potentiallyreversible, minimizing the damage that occurs if the quinone methide-nucleicacid conjugates briefly bind the wrong DNA sequence. This could open doors forthe development of less toxic, targeted chemotherapies that are effective atlower doses
A protein involved in transporting proteins and RNAs out of the cell nucleus offers an attractive target for treating cancer. In a review article, a team led by Qingxiang Sun and Da Jia from Sichuan University, China, discuss the role of the nuclear export factor CRM1 in cancer development. CRM1—which mediates the exit of molecular cargo out of the nucleus and into the cytoplasm—is overexpressed in tumors of the lungs, brain, liver and other organs, and its activity is associated with poor patient outcomes. Drugs that block CRM1 have been tested in clinical trials, with middling success. The authors outline a strategy for a new kind of CRM1 inhibitor that should produce fewer side effects and be less prone to drug resistance than existing agents.
Research elucidating how a protein suppresses the progression of liver cancer could provide new therapeutic targets, say researchers in China. A team led by Rong Xiang and Na Luo at Nankai University examined liver biopsies of patients with hepatocellular carcinoma (HCC), the third most common cause of cancer-related death worldwide. They also grafted HCC cells under the skin of mice. They found that a protein, called TIFA, suppresses the progression of HCC via one of three pathways. One involves competition with another protein, MALT1, to bind with the protein TRAF6, signaling pathways that induce cancer cell death. TIFA-induced cell death also results from suppressing MALT1. Finally, TIFA expression can also activate two genes, JNK and p38, which signal cell death and cell cycle arrest, respectively. The research may provide insights into drug targets that could affect HCC progression.
Treatment with aniron-transporting protein called transferrin could help reverse iron elevationin the Parkinsonian brain. David Finkelstein and colleagues from Australia'sUniversity of Melbourne compared post-mortem samples from 10 people withParkinson's disease and 10 individuals with no history of neurologicalproblems. They found that the substantia nigra region of the brain ofParkinson's patients had a 42% average elevation in iron deposits and a 35%average decrease in transferrin levels compared to the controls. In culturedneurons, adding transferrin helped traffic iron out of the cells. And in amouse model of Parkinson's, transferrin injections under the skin helped loweriron levels in the brain and improve motor symptoms of the disease. However,transferrin also caused iron depletion in the blood, leading to anemia, whichcould limit its therapeutic application in patients.
A new model for assessing disease progression of age-related macular degeneration (AMD) may improve the therapeutic responses of patients. The onset and progression of AMD — a leading cause of vision loss in seniors in developed countries — are linked to multiple genetic and environmental risk factors, including smoking and body mass index (BMI). Kang Zhang of University of California, San Diego with colleagues in the USA and China, has developed a prediction model by collecting data from three groups: patients with advanced AMD, those with intermediate AMD and a normal group. The researchers combined data for genetic variations within 15 genes previously linked to AMD risk with smoking status and BMI of individuals in the three groups. This resulted in a highly predictive model for AMD progression that is promising for improving personalized therapy of patients.
張康教授等在自然出版社與川大華西醫院生物治療國家重點實驗室聯合主辦的 《Signal Transduction and Targeted Therapy》（STTT）上發表了關于年齡相關性黃斑變性(AMD)疾病預測模型的文章(http://www.nature.com/articles/sigtrans 201616)，閱讀全文鏈接見最后。 這篇文章建立的預測模型可以給臨床上的黃斑變性(AMD)疾病診斷、治療和預后判斷等提供依據。