microRNA against tumor resistance to therapy
Incurable cancer returned vulnerability to drugs
Molecular biologists from the Georgia Institute of Technology were able to overcome the drug resistance of a pancreatic tumor by increasing the content of a certain type of microRNA in malignant cells. These molecules regulate the activity of genes responsible for cancer's immunity to chemotherapy. The results of the study are published in the journal Cancer Gene Therapy (Schreiber et al., Evidence for the role of microRNA 374b in acquired cisplatin resistance in pancreatic cancer cells).
In their experiments, the scientists subjected the culture of human adenocarcinoma cells to repeated action of cisplatin, a cytotoxic drug used in chemotherapy. Each time the dose of the drug was increased, allowing the surviving cells to multiply. After about a year, the researchers obtained malignant cells resistant to cisplatin. Their immunity to chemotherapy was 15 times greater than that of the original cancer cells.
Using a statistical method known as the hidden Markov model, biologists have identified genetic changes that could cause drug resistance. Scientists compared the number of two thousand microRNAs in cisplatin-resistant and baseline cell lines and found 57 types of compounds that were activated or, conversely, suppressed. At the same time, miR-374b – microRNA was isolated, which most likely controlled the genes that cause resistance to therapy.
Additional experiments have shown that an increase in the level of miR-374b in malignant cells makes the tumor more susceptible to drugs.
microRNAs are short RNA molecules whose length is approximately 20 nucleotides. They do not carry information about proteins like informational RNA, but they play a regulatory role by suppressing gene expression. One microRNA is able to control the activity of several genes performing coordinated functions.
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30.05.2016