Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells.

Abstract

Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. We previously found that HOX transcript antisense RNA (HOTAIR) is a negative prognostic factor and exhibits oncogenic activity in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the role and molecular mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel-7402 HCC cell line. The results showed that 129 genes were significantly down-regulated, while 167 genes were significantly up-regulated (fold change >2, p < 0.05). Bioinformatics analysis indicated that RNA binding proteins were involved in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and Bel-7402 cells increased the mRNA and protein expression levels of RNA binding motif protein 38 (RBM38). Moreover, the expression levels of RBM38 in HCC specimens were significantly lower than paired adjacent noncancerous tissues. In addition, knockdown of HOTAIR resulted in a decrease of cell migration and invasion, which could be specifically rescued by down-regulation of RBM38. Taken together, HOTAIR could promote migration and invasion of HCC cells by inhibiting RBM38, which indicated critical roles of HOTAIR and RBM38 in HCC progression.

• Authors: Chaofeng Ding, Shaobing Cheng, Zhe Yang, Zhen Lv, Heng Xiao, Chengli Du, Chuanhui Peng, Haiyang Xie, Lin Zhou, Jian Wu, Shusen Zheng
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 15 Issue 3 Pg. 4060-76 (Mar 06 2014) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 24663081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD82 protein, human
• HOTAIR long untranslated RNA, human
• Kangai-1 Protein
• QKI protein, human
• RBM38 protein, human
• RNA, Long Noncoding
• RNA-Binding Proteins

Topics

• Blotting, Western
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Down-Regulation (genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Hep G2 Cells
• Humans
• Kangai-1 Protein (genetics, metabolism)
• Liver Neoplasms (genetics, metabolism, pathology)
• Neoplasm Invasiveness
• Oligonucleotide Array Sequence Analysis
• RNA Interference
• RNA, Long Noncoding (genetics)
• RNA-Binding Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction