Abstract B38: Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application

Abstract

Background: Circulating nucleic acids (CNAs) are extracellular nucleic acids found in cell-free sera, plasma and other bodily fluids of healthy subjects and cancer patients. We have previously demonstrated that human serum or plasma contains microRNAs (miRNAs) and long non-coding RNA (lncRNAs) that are significantly up-regulated or down-regulated in various types of cancer and are of good diagnostic value for screening. The mechanisms underlying the stability of serum RNAs are unclear; lncRNAs may be protected by extracellular vesicles (EV) including apoptotic body (AB), microvesicle (MV) and exosome (EXO), as for circulating miRNAs. In order to find optimal method to evaluate the potential utility of circulating lncRNAs for cancer diagnosis or prognosis, more exploration should be undertook for the distribution of circulating lncRNAs. Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In serous vesicles of both colorectal cancer and healthy subjects, 17 of the 39 cancer-related lncRNAs were detected, including TDRG1, MEG3, DSCAM-AS1, 7SK, MIR31HG, CBR3-AS1, TUG1, BCAR4, EPB41L4A, PCA3, FAS-AS1, SUMO1P3, uc338, PRNCR1, PTENP1 and CUDR. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV. Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In sera of both colorectal cancer and healthy subjects, 16 out of the 39 cancer-related lncRNAs were detected. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV. Conclusions: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured lncRNAs, while the MVs contained the least amount of lncRNAs. EXOs, as their intercellular origin, have reasons to contain higher amount of lncRNAs among serous vesicles and seem to be the most promising research materials in the field of circulating lncRNA. Citation Format: Dong Lei, Lin Wanrun, Qi Peng, Xu Midie, Du Xiang. Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B38.