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.