Dysregulation of long noncoding RNAs (lncRNAs) has been implicated in a variety of human diseases including cancer. However, the function of lncRNA in the regulation of c-Myc oncogenic activity is still not well understood.

In a study published in PNAS, a research team led by Prof. MEI Yide from the School of Life Sciences, University of Science and Technology of China of the Chinese Academy of Sciences reported the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target.

c-Myc is activated in over half of human cancers and its oncogenic function has been largely attributed to its intrinsic nature as a master transcription factor. Given that the intracellular protein c-Myc is still indispensable in normal cells, the researchers switched the direction from simply inhibiting its function to finding the precursor or successor in its process of promoting cancer.

Through database analysis and experimental verification, they identified a new long noncoding RNA with abnormally high expression and cancer-promoting functions in various types of tumors including lung, breast and colon carcinomas, and named it E2F1 mRNA stabilizing factor (EMS, the same abbreviation of Express Mail Service, as they both send messages).

EMS as a direct transcriptional target of c-Myc could mediate the role of c-Myc in promoting tumor formation by controlling cell cycle function. Mechanistically, EMS associates with the RNA binding protein RALY, thereby stabilizing the mRNA of the cell cycle key regulator E2F1 and enhancing its protein expression level, ultimately promoting the G1/S cell cycle and the rapid proliferation of tumor cells.

Besides, the researchers found that as a transcriptional target of c-Myc, lncRNA E2F1 messenger RNA (mRNA) stabilizing factor regulates c-Myc function via modulating E2F1 mRNA stability.

This study clarified that EMS, a long noncoding RNA, can act as a messenger molecule to transmit c-Myc's cancer-promoting signal, providing a new perspective for understanding the molecular basis of c-Myc to promote tumor formation, and suggesting that EMS may be used as a new potential target in tumor treatment.

To find other cancer promoting mechanisms, further study on EMS will be carried out by this research team. “We hope our research can make sense to help human win in the war with cancer,” said Prof. MEI.

The action mechanism of EMS. (Image by MEI Yide’s team)