Health & Medical, Singapore (Commonwealth Union) – Transcription factors play a crucial role in regulating gene expression, and controlling the production of proteins necessary for cellular processes. Among the myriad of transcription factors, TOX2 (Thymocyte Selection-Associated High Mobility Group Box Protein 2) has emerged as an intriguing and relatively less-explored member of this diverse family. With its intricate mechanisms and potential implications in various biological contexts, TOX2 holds promise for deeper insights into cellular regulation. This article aims to shed light on TOX2 and its significance in gene regulation and its potential implications in health and disease.
TOX2 is a transcription factor belonging to the TOX protein family, which also includes TOX4 and TOX3. These proteins contain a conserved high mobility group (HMG) box domain that enables them to bind to DNA. TOX2, specifically, was initially identified as a gene associated with thymocyte selection during T-cell development. However, recent research has uncovered its presence and functions in other cell types and tissues as well.
Scientists from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) have found that the transcription factor, TOX2, was abnormally elevated in patients that had Natural killer/T-cell lymphoma (NKTL). An elevation in the TOX2 level brings about the growth and spread of NKTL, along with an overproduction of PRL-3, which is an oncogenic phosphatase that is a recognized significant component in the survival and metastasis of various other kinds of cancers. This is a major step forward in the discovery that provides a possible novel therapeutic target for the treatment of NKTL.
NKTL is an Epstein-Barr virus (EBV) linked, aggressive non-Hodgkin lymphoma (NHL) that has really poor treatment results during the advanced stages. The condition is known to be more frequent in Asia and Latin America compared to Europe and North America where it is much less frequent. In spite of the treatments of radiation therapy and chemotherapy for NKTL patients, they are regularly linked with an increased relapse rate as well as harmful side effects. As a consequence, the increased knowledge of the molecular mechanism that brings about the NKTL progression, along with the formation of novel targeted therapy strategies, has an urgent requirement for solutions as indicated by the scientists of the study.
Professor Chng Wee Joo as well as Associate Professor Takaomi Sanda of CSI Singapore, together with Dr Ong Choon Kiat from Duke-NUS Medical School, made public their significant breakthrough in a paper that appeared in the scientific journal Molecular Cancer in April this year. The collaborative measures from Dr. Jianbiao Zhou, Dr. Tze-King Tan, Ms. Sabrina Hui-Min Toh, and Miss Sinan Xiong, together with others in the team, have played a role in these significant findings.
These findings were the 1st to demonstrate the part played by TOX2 and PRL-3 in NKTL as well. Study findings had validation in both cell lines as well as in a bigger set of patient tumor samples. On top of that, the researchers analyzed the clinical features of 42 NKTL cases in an independent cohort discovering that TOX2 was not just overexpressed in NKTL primary tumors, but is negatively linked with patient survival as well.
Right now, TOX2-specific inhibitors are not available. This will make the targeting of TOX2, or its downstream PRL-3, a valuable therapeutic intervention for NKTL patients while warranting more study in the clinic.
“Overall, treatment for NKTL patients remains a challenge in the clinic. Novel insight into the molecular mechanisms of this disease would guide the development of effective targeted therapies to improve the survival of NKTL patients, especially for those refractory or relapsed cases,” explained Dr. Jianbiao Zhou from CSI Singapore, the 1st author of the study.
In moving ahead, the researchers are presently testing novel agents to target TOX2 and PRL-3 in NKTL. The long-term ambition is to take these into clinical trials.
