LINC01608 activated by YY1 facilitate hepatocellular carcinoma progression by modulating the EGFR/ERK axis

Abstract

Background: Long non-coding RNAs (LncRNAs) have been demonstrated to associate with a variety of cancers. However, the mechanisms of LncRNAs in hepatocellular carcinoma (HCC) progression are still not fully clarified.Methods: LINC01608 expression level in HCC and adjacent normal tissues was detected by real-time-quantitively PCR (RT-qPCR) in clinical samples and in situ hybridization (ISH) in tissue microarray. Several functional assays were performed to determine the biological effects of LINC01608 in HCC cells in vitro, while subcutaneous xenograft models and lung metastasis models in nude mice and immunohistochemistry (IHC) results showed the role of LINC01608 in HCC progression in vivo.The combination of LINC01608 with miR-875-5p and target genes was elucidated by dual-luciferase report assays, RNA immunoprecipitation (RIP) assays and fluorescence in situ hybridization (FISH) assays. Finally, bioinformatics analysis and chromatin immunoprecipitation (CHIP) were performed to investigate the mechanism of Yin Yang-1 (YY1) regulating LINC01608 transcription.Results: LINC01608 was overexpressed in HCC tissues, and high LINC01608 expression predicted poor overall survival (OS) and disease-free survival (DFS) in HCC patients. LINC01608 could promote HCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated that LINC01608 could sponge to miR-875-5p and activate the EGFR/ERK pathway. Moreover, we identified transcriptional factor YY1 could bind to the promoter of LINC01608 and induce its transcription. Conclusion:LINC01608 could serve as a promising prognostic biomarker of HCC. YY1-activated LINC01608 could promote HCC progression by associating with miR-875-5p to induce the EGFR/ERK signalling pathway. This discovery might provide therapeutic strategies for HCC.

MicroRNA-875-5p inhibits the growth and metastasis of cervical cancer cells by promoting autophagy and apoptosis and inhibiting the epithelial-mesenchymal transition

“…This allows the detachment of cells from the primary tumor and the separation of surrounding tissues and distant organs (41). Recent studies have shown that miR-875-5p plays an important role in influencing the EMT behavior of cancer cells (22,42). In vitro experiments revealed that inhibition of miR−875−5p promotes tumor growth and metastasis by promoting HCC cell epithelial−to−mesenchymal transition progression (22).…”

“…An important finding is that overexpression of miR-875-5p promoted autophagy in CC cells, a novel mechanism by which miR-875-5p suppresses the growth of CC. To our knowledge, this is the first study exploring the correlation between miR-875-5p expression level and autophagy of CC cells, despite the involvement of miRs in other types of cancer (41)(42)(43)(44)(45)(46). Autophagy is a highly conserved catabolic process that plays a fundamental role in maintaining cellular homeostasis (43).…”

6-O-endosulfatases in tumor metastasis: heparan sulfate proteoglycans modification and potential therapeutic targets

“…Apart from the signaling pathways mentioned above, other HS-binding growth factors can be modulated by SULFs as well. EGFR is the transmembrane receptor for various ligands including epidermal growth factor (EGF), heparinbinding EGF (HB-EGF), transforming growth factor α (TGF-α) and amphiregulin (AR) [80]. SULF1-mediated desulfation of cell surface HSPGs has been implicated in the reduction of EGFR phosphorylation, leading to the inhibition of tumor metastasis [81,82].…”