Identification of Novel Long non-coding RNAs and Expression Analyses in Rectal Neuroendocrine Tumors

Altered expression of long-non-coding RNAs (lncRNAs) is associated with various pathological conditions, including cancers. LncRNAs associated with rectal neuroendocrine tumors (rNETs) remain unexplored. Here, we report the identification of 418 high confidence novel lncRNAs by analyzing publicly available RNA-Seq datasets of primary rNETs and rNETs with lymph node or liver metastases. Novel lncRNAs had basic characteristics similar to the known lncRNAs and showed individual-specific expressions. Expression analysis in the normal rectal mucosa and pancreas NETs (pNETs) and small intestine NETs (siNETs) revealed high expression of two lncRNAs, namely MSTRG30689.1 and MSTRG341161.1. Functional characterization revealed that 9 lncRNAs could work as the ce-RNA and one as miRNAs precursor. Cis- and trans- analysis of the 9 PCG-associated lncRNAs revealed that these lncRNAs could regulate various important cancer-related genes. Further, an integrated regulatory mechanism for selected cancer hallmark genes such as SMAD3, ZEB1, TCF4 and ATM through lncRNAs is predicted. Taken together, our analyses reveal common and unique lncRNAs associated with rNETs and their metastatic variants, their PCG targets, and predict mechanisms of lncRNA mediated regulation of target PCGs.