SNU has identified a protein that represses genetic regulators linked to the development of cancer, adding detail to the complex picture of how tumors arise and grow.

A group of researchers led by V. Narry Kim unveiled how one type of RNA-binding proteins, Lin28, control the expression of micro-RNAs called let-7 in a recent study published by peer journal, Molecular Cell. The findings could eventually lead to new ways in the treatment of cancer, Kim said.

Micro-RNAs are tiny pieces of genetic material that target and suppress the activities of other genes. The material was first discovered in the 1990s and recent studies found they play a major role in the development of cancer.

Although there has been a wealth of studies on the birth and maturation of micro-RNAs, the regulatory mechanisms and death process have remained largely unknown.

In their recent study, Kim and her colleagues suggested that the Lin28 proteins dictate the growth and suppression of let-7 RNAs based on experiments of liver cancer cell lines and embryonic stem cells in laboratory mice.

The let-7 RNAs are known to function as tumor suppressors by targeting proteins such as RAS, HMGA2 and c-Myc, which can cause excessive cell proliferation and cancer without checks and balances.

Lin28 is an RNA-binding protein involved in gene expression and often found in certain types of cancer cells such as hepatocellular carcinoma (HCC), a primary type of liver cancer.

The mice were engineered not to produce Lin28 proteins themselves, which led to an increase in the detection of mature let-7 RNAs in the cells, although there were no changes to the level of pre-let-7.

This means that Lin28 is not involved in the birth of let-7 RNAs, but could repress their expression by interacting with pre-let-7, which then become susceptible to degradation.

``Although Lin28 has a role in the proliferation of embryonic stem cells, an excessive level of the proteins could prevent the development of mature let-7 RNAs and result in cancer,'' said Kim.

``In suppressing Lin28, or preventing them from interacting with pre-let-7, we could find new ways to prevent tumor development. The findings could also be adapted to stem cell programming by opening new opportunities in developing technologies to activate Lin28 in the state of embryonic stem cell development,'' she said.

October 27, 2008
SNU PR Office