A Catholic Medical Center (CMC) research team has found that by controlling a specific liver cancer suppressor gene, they could suppress liver cancer cells as well as tumor immunity activation mechanism.
|Professor Nam Seok-woo|
Professor Nam Seok-woo at the Catholic University of Korea and his team have been analyzing data on “Let-7i-5p,” a micro RNA included in the liver cancer suppressor gene HDAC6, to identify the mechanism that inhibits liver cancer cells and activates immune by inducing gene activity inhibited in liver cancer.
They found that histone deacetylases (HDACs) inhibited tumor cells, including tumor cell growth, metastasis, angiogenesis, and immunoregulatory mechanism of HDAC6. The researchers also confirmed that they could control liver cancer by controlling the mechanism of “HDAC6-Let-7i-5p-TSP1-CD47.”
HDAC6 is one of the HDACs enzymes mostly expressed in various carcinomas while contributing to tumor formation and development. Professor Nam’s team became the first research group to confirm that HDAC6 can also act as a tumor suppressor gene for liver cancer in 2012.
The researchers found out that HDAC6 was a therapeutic potential as a liver cancer inhibitor, but there have been little to no research on the mechanism. Based on the fact that HDAC6 is one of the representative progeny genetic modulators, they hypothesized that it could control various microRNAs that contribute to cancer development in normal hepatocytes.
Through this process, they could accurately find Let-7i-5p after screening for tumor-specific microRNAs that specifically increase when HDAC6 is lost or suppressed during liver cancer development.
Professor Nam also found that Let-7i-5p contributes to the development of liver cancer by inhibiting the protein translation of Thrombospondin-1, potent angiogenesis and tumor growth inhibitor in vivo.
“The study is the first of its kind to identify HDAC6 as a liver cancer inhibitor, and subsequently investigated the complex regulatory networks of tumor cells, immune cells, and hepatocytes in the tumor microenvironment,” Professor Nam said.
The results of the research were published in Hepatology.