Identification of MicroRNAs specific to hepatic cancer stem cells but not to normal stem cells by small RNA deep sequencing

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-30

* FARE Award Winner

Authors

• J Ji
• T Yamashita
• L Reid
• Y Song
• J Wei
• J Khan
• X Wang

Abstract

Drugs targeting cancer stem cells (CSCs) hold promise in eliminating cancer burden, but normal stem cells are likely to be targeted due to their similarities with CSCs. Hepatocellular carcinoma (HCC) is an aggressive and heterogeneous human malignancy attributed to the presence of hepatic CSCs (HepCSCs). Isolated EpCAM+ HCC cells are HepCSCs. We hypothesized that certain miRNAs are exclusively altered in HepCSCs and are ideal targets for developing effective HCC therapies. We used next generation sequencing technology to profile miRNAs. 16 small RNA libraries were made from: a) EpCAM+ HepCSCs and corresponding differentiated EpCAM- HCC cells; b) normal hepatic stem cells and their lineage restricted hepatoblasts; c) primary hepatocytes; d) pooled embryonic stem cells. In our analysis pipeline, 35 nucleotide-filtered reads were aligned to the reference human miRBase, then to the genome. The alignment yielded an average of 5.56 million high-quality uniquely mapped reads, of which 78.9% were aligned to miRBase. The miRNA profiles were then compared between EpCAM+ and EpCAM- cells to identify unique miRNAs specific to HepCSCs. The results show that 28 miRNAs were specifically altered in EpCAM+ HepCSCs. We are currently examining miRNA mutations associated with HepCSCs. The functions of these miRNAs in HepCSCs will be further explored.

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