HNRNPAB‐regulated lncRNA‐ELF209 inhibits the malignancy of hepatocellular carcinoma
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 (ln...
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Veröffentlicht in: | International journal of cancer 2020-01, Vol.146 (1), p.169-180 |
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Sprache: | eng |
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Zusammenfassung: | 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.
What's new?
Increased levels of the protein HNRNPAB can facilitate metastasis of hepatocellular carcinoma (HCC). But how does it do this? In this study, the authors found that HNRNPAB can repress a previously uncharacterized long noncoding RNA (lncRNA), called lnc‐ELF209. They then found that lnc‐ELF209 plays a crucial role in inhibiting the migration, invasion, and epithelial‐mesenchymal transition (EMT) of HCC tumor cells. Further analysis of this HNRNPAB‐lncELF209 regulatory axis should enhance our understanding of the molecular mechanisms involved in HCC, which may in turn lead to new therapeutic candidates. |
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ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.32409 |