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

Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells.
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DOI:
10.3390/ijms15034060
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发表时间:
2014-03-06
影响因子:
5.6
通讯作者:
Zheng S
Zheng S
中科院分区:
生物学2区
文献类型:
--
作者:
Ding C;Cheng S;Yang Z;Lv Z;Xiao H;Du C;Peng C;Xie H;Zhou L;Wu J;Zheng S

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长链非编码RNA HOTAIR在癌细胞的各种生物学过程中发挥调节功能,如增殖、凋亡、迁移和侵袭。我们以前发现HOX转录反义RNA(HOTAIR)是一个负预后因子,并在肝细胞癌(HCC)中表现出致癌活性。本研究旨在探讨HOTAIR促进肝癌细胞迁移和侵袭的作用及其分子机制。首先,我们利用基因芯片技术分析了Bel-7402肝癌细胞系中HOTAIR基因的表达谱。结果显示,129个基因表达显著下调,167个基因表达显著上调(倍数变化>2,p < 0.05)。生物信息学分析表明,RNA结合蛋白参与了这一生物学过程。RNA结合基序蛋白38(RBM 38)的mRNA和蛋白表达水平增加。此外,RBM 38在HCC标本中的表达水平显著低于配对的癌旁组织。此外,HOTAIR的敲低导致细胞迁移和侵袭的减少,这可以通过RBM 38的下调来特异性地挽救。综上所述,HOTAIR可通过抑制RBM 38促进HCC细胞的迁移和侵袭,这表明HOTAIR和RBM 38在HCC进展中起关键作用。
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.
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长非编码 RNA HOTAIR 是恶性肿瘤的驱动因素,可预测食管鳞状细胞癌的阴性预后并表现出致癌活性
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