Small molecules play an important role in reducing the spread of cancer

Scientists report that a small molecule that helps regulate gene expression plays an important role in securing our freedom from cancer.

In human lung cancer cells, they have shown low levels of microRNAs, miR-125a-5p, which cause abnormal cells like cancer cells to die, and are associated with high levels of the protein TIMP-1, which has been associated with TIMP-1 The prognosis of poor cancer patients.

Conversely, when they reduce the level of TIMP-1 in these highly fatal cancer cells, the tumor spreads and the cell death rate rises with the expression of miR-125a-5p, the Department of Cancer Biologist Mumtaz V. Rojiani Say. He has a Ph.D. in medicine from the Georgia Medical School and a member of the Molecular Oncology and Biomarker Program at the Georgia Cancer Center at Augusta University.The researcher's correspondent, Rojiani, said that although it is technically difficult to increase microRNA levels, further description of how cancer can hijack these normal body systems may help determine new treatment goals.

TIMP-1 has an active role in a healthy body and can help to balance the level of enzymes produced by the body, thereby reducing cell movement such as wound healing or reproduction. A healthy body and cancer make these enzymes, matrix metalloproteinases or matrix metalloproteinases, decompose the surrounding matrix and help maintain cell stability. Although positive factors such as wound healing are critical, it also allows cancer cells to move freely when the matrix breakdown is taken away by the cancer.The research coauthor Dr. Amyn M. Rojiani compared cancer cells to blueberries and compared the substrates to pancakes. "To make these blueberries move or become close to each other, they secrete enzymes, matrix metalloproteinases, and break down pancakes and matrices," said MCG Pathology and chairman of the Georgia Research Alliance's Outstanding Cancer Scientist.However, in cancer, the level of TIMP-1 rises dramatically. It has a unique role in both promoting the growth of new blood vessels and inhibiting apoptosis. If some cells cannot be cured, the cells will naturally die.

"In cancer, what tumor cells do is start to secrete more of these enzymes so that they can decompose the matrix and begin to migrate and metastasize," said Mumtaz Rojiani.Traditionally, TIMP-I should inhibit MMPs, but over the years it has been found to have other functions that actually increase tumor invasiveness.In their study of TIMP-1 expression in human lung cancer cells, they saw this positive reaction. It turns out that TIMP-1 is like a two-sided person. Sometimes it smiles at cancer and sometimes it cuts it off.MCG scientists found that breast cancer, gastric cancer, and colorectal cancer, as well as non-small cell lung cancer, have poor tumor spread and prognosis, elevated levels of two-sided TIMP-1, accounting for approximately 85% of all lung cancers, and a five-year survival rate lower than 20%.

Overexpression of TIMP-1 is also associated with increased upregulation of Bcl-2, which prevents apoptosis or cell death. To make bad things worse, the key way of chemotherapy is by inducing apoptosis, and TIMP-1 has been associated with potentially lethal drug resistance.

However, with the high expression of miR-125a-5p, TIMP-1 becomes a target. Dr. Sampa Ghoshal-Gupta, a postdoctoral researcher at MCG, and the lead author of the study, said one of the results was the increased expression of the p53 gene, a known tumor suppressor that causes cell death. In fact knocking down TIMP-1 also increases p53 levels.

They want to learn more about how, and Ghoshal-Gupta suspects there is more involved than protein-protein interactions. So they also started researching microRNAs and found that knocking out TIMP-1 in cancer cells affects many cells.