Investigating the MALAT1 Gene’s Potential to Treat or Prevent Multiple Myeloma

Lerner Research Institute’s Jianjun Zhao, MD, PhD, was recently awarded a two-year, $200,000 grant from the V Foundation for his research on the genetic underpinnings of multiple myeloma.

Multiple myeloma is the second most frequently diagnosed blood cancer in the United States, affecting nearly 30,000 new patients each year. It affects the blood’s plasma cells (white blood cells that play an important role in the body’s immune system), which typically collect in the bone marrow. While treatments can help manage the disease, and have lengthened the average time of survival to around five years, there is currently no cure.

The V Scholar Award, which recognizes young tenure-track scientists conducting promising basic and translational cancer research, will help propel Dr. Zhao into the next phase of his career, which has been committed to investigating these new treatments that are so desperately needed.

Specifically, Dr. Zhao will use the funds to investigate the viability of targeting a gene called MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) to treat or prevent multiple myeloma.

About MALAT1, a type of non-coding RNA

MALAT1 belongs to a class of genes called long non-coding RNA, which are not transcribed into proteins but instead regulate how other genes are transcribed. Specifically, MALAT1 regulates the expression of growth control- and metastasis-related genes.

In addition, MALAT1 functions to help repair broken DNA strands. “We see that MALAT1 mends the DNA using a special alternative mechanism that is particularly prone to error and has not been well studied in the context of multiple myeloma,” says Dr. Zhao. “My team is working to investigate how this mechanism contributes to the onset and progression of the disease, as we believe MALAT1 levels may serve as a predictor of multiple myeloma.”

Dr. Zhao’s research suggests that MALAT1 levels are elevated in tumors and that this overexpression promotes the development of multiple myeloma tumors. They found that inhibiting the activity of MALAT1 induced DNA damage and programmed cell death, two responses that can help stop the spread of cancerous cells. In this way, MALAT1 inhibitors may be a potential new treatment option to explore.

Studying how MALAT1 may protect against multiple myeloma

This award will help Dr. Zhao continue his work to understand the specific cellular and molecular mechanisms by which MALAT1 may protect against multiple myeloma, studying MALAT1’s binding patterns and the effects of these interactions. He will also look for innovative and targeted ways to deliver a potential MALAT1 inhibitor. Dr. Zhao is currently investigating the feasibility of using a carbon nanotube to deliver an anti-MALAT1 molecule directly into the tumor microenvironment.

The V Foundation, founded by ESPN and famous college basketball coach and commentator Jim Valvano, seeks to find a cure for cancer by supporting research and raising awareness about the importance of funding and conducting cancer research. Since its creation in 1993, the foundation has awarded over $200 million dollars to cancer researchers and programs across the country. The V Foundation honors Jim’s legacy as he sadly lost his own battle with cancer just months after its founding.

Dr. Zhao is assistant staff in the Department of Cancer Biology. He joined Cleveland Clinic in 2015, coming from Dana-Farber Cancer Institute in Boston, Massachusetts. Dr. Zhao is also a member of the Case Comprehensive Cancer Center, specifically the Hematopoietic and Immune Cancer Biology Program. He has been co- or first author on many publications in respected journals including Science Translational Medicine, Leukemia and Blood.