The 14th symposium

Speech

Special　Lecture1

“Epigenetic control of breast cancer by non-coding RNAs”
Noriko Saitoh, Chief, Division of Cancer Biology, The Cancer Institute of Japanese Foundation for Cancer Research

Approximately 70% of breast cancers are estrogen receptor (ER)-positive. These cancers respond to endocrine therapy, but they pose a problem because they frequently recur. The molecular mechanism of this cancer needs to be determined. We found that long non-coding RNAs (Eleanors) are expressed in the nucleus of human ER-positive recurrent breast cancer cells, that “clouds” of Eleanors (clusters of non-coding RNAs and liquid droplets) are formed in the nucleus, and that transcription of the ESR1 gene (which encodes an ER) is activated. Eleanors delineate a 0.7-Mb topologically associating domain (TAD) containing the ESR1 gene and they control the 3-dimensional structure of genomic DNA. Eleanors link that TAD and another TAD containing the FOXO3 gene, which is 42.9 Mb away from ESR1, to activate transcription in a coordinated manner, thus balancing cell growth (ESR1) and apoptosis (FOXO3). As a result of analyzing tissue in cancer foci and metastases from breast cancer patients, we also found that Eleanors are related late recurrence. Our findings have indicated that Eleanors might serve as a target for diagnosis and treatment.

Special　Lecture2

“Elucidation of the mechanisms of pancreatic carcinogenesis by repetitive RNAs and their clinical use for cancer screening”
Motoyuki Otsuka, Lecturer, Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo

Pancreatic cancer is intractable at present, and its incidence has increased over the past few years. In order to improve the prognosis for pancreatic cancer, identification of novel biomarkers that allow early detection of the cancer and the development of the preventive methods against the malignant transformation of normal pancreatic cells are urgently required, based on the elucidation of the mechanisms of its carcinogenesis. It was reported that some non-coding RNAs that have repetitive sequences, known as “repetitive RNAs”, which are not expressed in normal pancreatic tissues, are highly expressed in pancreatic cancer tissues. Thus, we analyzed the biological functions of such repetitive RNAs during the pancreatic carcinogenesis and proposed a new molecular mechanism of pancreatic carcinogenesis. In addition, we developed a highly sensitive method (TRAP-digital PCR method) to detect such RNAs in patients’ sera and are validating its effectiveness in pancreatic cancer screening. Because those repetitive RNAs are expressed from the heterochromatin regions of the human genome in which RNAs are usually not transcribed in the normal state, some epigenetic mechanisms are probably involved in the abnormal expression of such repetitive RNAs. However, its precise mechanisms remain to be elucidated. In this lecture, our latest results about these mysterious repetitive RNAs in pancreatic cancer will be discussed.