HNRNPAB-regulated lncRNA-ELF209 inhibits the malignancy of hepatocellular carcinoma
HNRNPAB-regulated lncRNA-ELF209 inhibits the malignancy of hepatocellular carcinoma
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HNRNPAB 调节的 lncRNA-ELF209 抑制肝细胞癌的恶性肿瘤。
DOI：
10.1002/ijc.32409
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发表时间：
2020-01-01
影响因子：
6.4
通讯作者：
Dai, Zhi
中科院分区：
文献类型：
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作者：
Yang, Yi;Chen, Qing;Dai, Zhi
我们前期的研究表明，HNRNPAB是促进肝细胞癌（HCC）转移的关键基因。然而，这种关系背后的分子机制尚不完全清楚。在我们的研究中，我们利用长链非编码RNA （lncRNA）微阵列鉴定了一种名为lnc-ELF209的hnrnpap调控的lncRNA。我们从染色质免疫沉淀实验中发现，HNRNPAB通过直接结合lnc-ELF209的启动子区域来抑制lnc-ELF209的转录。我们还通过实时定量聚合酶链反应、RNA原位杂交和免疫组织化学分析了HCC患者和细胞系的临床样本，发现HNRNPAB与lnc-ELF209的表达呈负相关。上调/下调实验和拯救实验表明，lnc-ELF209抑制HNRNPAB调控的细胞迁移、侵袭和上皮-间质转化。这提示了hnrnpab促进HCC进展的一种新的调控机制。采用RNA pull-down和LC-MS/MS检测三磷酸异构体酶、热休克蛋白90- β和波形蛋白是否参与了lnc-ELF209的肿瘤抑制功能。此外，我们发现lnc-ELF209能够稳定TPI蛋白的表达。我们还发现lnc-ELF209在HCCLM3细胞中的过表达导致肺转移率较低，这表明HCC表型的侵袭性较低。总的来说，这些发现为HNRNPAB促癌活性的调控机制提供了新的见解，并证明lnc-ELF209是HNRNPAB调控的lncRNA，可能在抑制HCC进展中发挥重要作用。
Our previous study demonstrated that heterogeneous nuclear ribonucleoprotein AB (HNRNPAB) is a key gene that facilitates metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms behind this relationship are not fully understood. In our study, we utilized long-noncoding RNA (lncRNA) microarrays to identify a HNRNPAB-regulated lncRNA named lnc-ELF209. Our findings from chromatin immunoprecipitation assays indicate that HNRNPAB represses lnc-ELF209 transcription by directly binding to its promoter region. We also analyzed clinical samples from HCC patients and cell lines with quantitative real-time polymerase chain reactions, RNA in situ hybridization and immunohistochemistry, and found that there is a negative relationship between HNRNPAB and lnc-ELF209 expression. Up/downregulation assays and rescue assays indicate that lnc-ELF209 inhibits cell migration, invasion and epithelial-mesenchymal transition regulated by HNRNPAB. This suggests a new regulatory mechanism for HNRNPAB-promoted HCC progression. RNA pull-down and LC-MS/MS were used to determine triosephosphate isomerase, heat shock protein 90-beta and vimentin may be involved in the tumor-suppressed function of lnc-ELF209. Furthermore, we found lnc-ELF209 could stabilize TPI protein expression. We also found that lnc-ELF209 overexpression in HCCLM3 cell resulted in a lower rate of lung metastatic, which suggested a less aggressive HCC phenotype. Collectively, these findings offer new insights into the regulatory mechanisms that underlie HNRNPAB cancer-promoting activities and demonstrate that lnc-ELF209 is a HNRNPAB-regulated lncRNA that may play an important role in the inhibition of HCC progression.