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.

Propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR/p70S6K signaling pathway in melanoma cells

“…The expression of HOTAIR in hepatocellular carcinoma is high and close to non-tumor tissues, which indicates that the expression of HOTAIR in hepatocellular carcinoma is associated with lymph node metastasis (19). In a previous study, which knocked out HOTAIR in hepatocellular carcinoma cells, it was found that matrix metalloproteinase-9 (MMP-9) was also knocked out, which indicated that MMP-9 is likely to be involved in the regulation of hepatocellular carcinoma progression (20).…”

Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

“…Zhang et al [32] showed that HOTAIR accelerated carcinogenesis in hepatitis B-infected liver. Ding et al [33] showed that HOTAIR promote the migration and invasion of HCC cells, while Ishibashi et al [34] showed that HOTAIR expression is associated with HCC progression. A recent study showed that HOTAIR enhances the methylation of PTEN and contributes to liver fibrosis [21], providing some additional clues about the regulatory effect of HOTAIR associated with PTEN.…”

“…Taken together, these results imply the involvement of HOTAIR in the pathogenesis of NAFLD. And based on previous studies concerning the roles of HOTAIR in HCC [33,34], it could be inferred that HOTAIR may play an important role in the disease progression from NAFLD to HCC. Nevertheless, additional studies are necessary to confirm the results and the hypothesis.…”

Roles of long noncoding RNAs in Hepatocellular Carcinoma

“…Simultaneously, HOTAIR is required for the occupancy of suppressor of zeste 12 homolog (SUZ12, PRC2 subunit) on MIR-34A loci [34], then epigenetically modify their targeted genes, including Snail and vimentin (Figure 2b). HOTAIR also could promote migration and invasion of HCC cells by inhibiting RBM38 [35] (Figure 2d). H19 can specifically associate with enhancer of zeste homolog 2 (EZH2), a key subunit of the PRC2 complex, and inhibit E-cad expression by directly suppressing E-cad transcription and by indirectly activating Wnt signaling [36] ( Figure 2e); H19 associated with the protein complex hnRNP U/ PCAF/RNAPol II, activating miR-200 family by increasing histone acetylation.…”