Clin Epigenet: Specific Epigenetic Markers Expected to Reveal Mechanisms of Progression and Metastasis in Various Cancers

In a recent study published in the Clinical Epigenetics entitled "Characterization of DNA methylation changes in EBF3 and TBC1D16 associated with tumor progression and metastasis in multiple cancer types," scientists from the University of Otago have identified a variety of cancer cell biomarkers that may help clinicians identify which cancer cells are more likely to spread to other parts of the body.

The results of this study may provide clinicians and patients with more clear ideas to elucidate the mechanism of cancer cell spread and how to use effective therapies for the treatment of different types of cancer at a later stage. Early detection of the rate of cancer spread may help improve the prognosis of cancer patients, said researcher Euan Rodger.

In most patients who die of cancer, the spread of cancer from one organ to another is often considered highly lethal, and tracking the spread of cancer has become an important weapon against cancer. In the study, researchers wanted to see if new molecular changes existed in other types of cancer cells, albeit with some confusion, but in general, the researchers got the answers they wanted.

Based on the results of this study, the researchers are expected to develop novel strategies to track the therapeutic effects of cancer patients in the future; next, researchers will also continue to conduct in-depth studies to find more epigenetic markers to reveal the mechanisms of progression and metastasis of many types of cancer.

Proteins Identified as Key to Stem Cell Production

A multinational team of scientists led by Professor Benjamin Blencowe of the University of Toronto has identified proteins that play a key role in the control of pluripotency, which may mean a possible breakthrough in the production of so-called induced pluripotent stem cells.

Induced pluripotent stem cells are of great value for medical research because they can flexibly develop into many different types of cells. However, producing these cells is challenging because the proteins that control their production are largely unknown

The team discovered these proteins using a tiling code developed by Professor Blencowe several years ago.

"The mechanisms that control embryonic stem cell pluripotency have been a mystery for some time," explains Dr. Brendan Frey, also from the University of Toronto, who co-authored the study published in the journal Nature.

"However, Professor Blencowe and his team found that the proteins identified by our splicing code can activate or reduce the pluripotency of stem cells."

"Suppose you've tasted a lot of delicacies, but you have no idea what it takes to make them. Then, one day, you will find that all gourmet food cooks will use something called a "measuring cup". Now you know important information about how to prepare dishes, and you know the "control knobs" that can be turned to make different dishes, just as adjusting the amount of butter and flour produces different kinds of pastries.

Dr Frey said: "Although the complete formula for producing induced pluripotent stem cells may not yet be available, it looks more likely at first."

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Nature: Protein OTX2 Plays a Crucial Role in Germ Cell Development

In a new study, researchers from the University of Edinburgh in Scotland, Shandong University in China, and the Institute of Genetics and Biophysics in Naples, Italy, discovered key insights into how sperm cells (ie, sperm) and egg cells (eggs) are formed, thus helping to reveal their earliest stages of development. This study is the first to show how proteins affect the fate of these cells that determine the DNA profile of the offspring. The relevant research results were published online in the Nature recently, and the paper titled "OTX2 restricts entry to the mouse germline".

These findings focus on the development of germ cells that produce sperm and eggs. During reproduction, germ cells from different sexes fuse together to form new individuals.

These researchers used mice as the research object to explore the first stage of germ cell formation. They focused on a molecule called BMP4 that was found to block the activity of Otx2, a gene regulator that directs the development of non-germ cells (called somatic cells). They demonstrated that lowering Otx2 activity by BMP4 is critical for germ cell development.

Professor Ian Chambers of the University of Edinburgh said, "Before, the study of germ cell identity focused on a series of events that occurred during germ cell development. We are now able to begin to observe early events that occur during germ cell development. These exciting discoveries open the door to a better understanding of the earliest stages of controlling the separation of germ cells from all other cells."

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Nat Commun: New Ways to Reduce the Side Effects of Cancer Drugs

Protein research is one of the hottest areas of medical research because protein-based drugs can be developed to treat diabetes, cancer and other diseases.

Although proteins have great potential, their incredibly complex chemical structures pose enormous challenges for scientists. As a result, researchers have been looking for a tool to modify them more precisely, thereby reducing the side effects of the drug.

Recently, researchers have developed a new protein modification method that can reduce the side effects of drugs and can be the key to promoting the development of protein drugs. Their research has been published in Nature Communications.

Protein structure is like an intricate yarn ball

Researchers call this method "His-tag acetylation." In addition, it can add toxic molecules to proteins that attack diseased cells in the body of cancer without attacking healthy cells.

“Protein is like a ball of yarn. When they are opened, a long chain of amino acids will appear. This new modification allows us to precisely target these intricate structures. In short, it will help the drug production, and we can make changes more confidently so that we can reduce side effects in the future," the author said.

Modified proteins must be pinpointed

His-tag acylation accurately targets these complex yarn-like protein structures, which also makes it possible to produce drugs with novel properties.

For example, researchers can now attach fluorescent molecules to proteins, allowing microscopy to track the path of proteins through cells. Since the primary function of these proteins is to transport anticancer molecules around the diseased cells, it is important to follow their path carefully throughout the body.

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Molecular Cancer: Researchers Find New Targets for Breast Cancer

A study led by Dr. Suresh Alahari, professor of biochemistry and molecular biology at the University of Louisiana Health Science Center (LSU Health), first discovered that a small piece of RNA can dysregulate cellular energy metabolism, which is a major feature of cancer. These findings have found a new target for therapeutic intervention in breast cancer, and the findings are recently published in Molecular Cancer.

MicroRNAs are a class of single-stranded small RNA molecules that play important regulatory roles in cell biology, and they bind to target genes to reduce their function. MicroRNAs can be used both as a carcinogen and as a tumor suppressor.

The research team has previously found that miR-27b is a breast cancer carcinogen, and researchers have found it to be high in breast cancer tissue. In this study, the researchers found that this molecule inhibited the production of a protein called PDHX. PDHX involves cellular metabolism, and cellular metabolism can affect cell proliferation. Lack of PDHX means that cells can rapidly produce new cells and promote tumor growth and progression. The team found a significant reduction in PDHX levels in breast cancer cells.

"Based on these data, we believe that inhibition of miR-27b is a new treatment for breast cancer," Dr. Alahari said. "Inhibition of miR-27b promotes PDHX expression, which inhibits tumor proliferation through several established metabolic cascades."

According to NCI statistics, the number of new breast cancer patients in the United States will be higher than other cancers in 2018. NCI estimates that there will be 266,120 new cases of breast cancer, and 40,920 will die from breast cancer. "The use of microRNA analogs or anti-microRNA agents will counteract their function, and reversing oncogene metabolism will be a unique cancer treatment strategy. Potential clinical applications of miRNAs include diagnostic tests, disease prevention, and prognostic markers, which make miRNAs a unique and attractive option for reducing cancer morbidity and mortality."

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CDK6—the Hot Potato in Cancer Treatment

It is well known that the formation of tumors is a multi-step process in which cells acquire genetic and epigenetic changes during tumorigenesis and eventually reach a state of complete transformation. The cell cycle kinase CDK6 has received a lot of attention in the past few years. It is not only a cell cycle-dependent kinase but also a transcriptional regulator with functional characteristics different from the same family of CDK4. CDK6 regulates the expression of many genes, and some studies have found that this molecule can promote the development of malignant blood diseases such as AML and ALL, and is also important for the self-sustaining of hematopoietic stem cells and leukemia stem cells.

Recently, researchers from Vienna reported that CDK6 is able to antagonize p53-induced responses. Previous studies have found that high and low expression of CDK6 are associated with poor prognosis, but the reasons for this have not been revealed. In this study, the researchers found that CDK6 promotes tumor formation by regulating transcriptional responses at specific stages. In the early stages of tumorigenesis, CDK6 kinase prevents p53 from acting in hematopoietic cells by inducing a complex transcriptional program. Cells lacking CDK6 kinase function require the presence of TP53 mutations to achieve a fully transformed immortal state.

The researchers found that CDK6 binds to promoters of many genes, including p53 antagonists Prmt5, Ppm1d and Mdm4. The researchers said the findings of the study were also confirmed in patients: the frequency of TP53 mutations in tumors expressing low levels of CDK6 was higher than expected. The study found that CDK6 can promote cell cycle progression to antagonize stress responses and affect the effects of p53 and RB. Specific inhibition of CDK6 kinase activity results in cells more susceptible to p53-induced cell death and also stimulates the growth of p53 mutant clones in precancerous cells.

EiF4E and Depression

A recent study about changes in the brain linked to depression paved the way for new therapies. Moreover, the study also revealed why a certain antidepressant drugs stop working in some people.

Scientists from the University of Edinburgh studied mice that were bred to have defects in their ability to activate a certain molecule, called eIF4E. And it turned out that those animals showed signs of depression, reduced levels of hormone serotonin and also disinterest in food.

Treatment with a commonly prescribed antidepressant called fluoxetine failed to produce a response in the mice. This suggests that activation of eIF4E is required for the beneficial antidepressant effects of fluoxetine, which belongs to a category of medicines called selective serotonin re-uptake inhibitors (SSRIs). (sciencedaily.com)

This, however, could help explain why some patients stop responding to SSRIS. Previous studies have shown the effect of eIF4E in regulating protein synthesis in the brain. And the defects of eIF4E are also linked to other neurological conditions. But it is the first time it has been found to be connected with depression.

Those findings, according to the scientists, could help develop novel therapy for depression, which are affecting increasing numbers of people worldwide.

Dr Christos Gkogkas, a Chancellor's Fellow in the University of Edinburgh's Center for Discovery Brain Sciences, stated: “Our investigation uncovers that changed protein synthesis through eIF4E is a key cellular process in the brain that can go amiss in depression. Imperatively it might clarify why a few people with depression wind up resistant to treatment with SSRIs. This information can enable us to plan another generation of antidepressants.”

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