Abstract
BackgroundThe lncRNA LINC00460 plays crucial roles in several epithelial cancers, although its mechanisms of action differ greatly in different cellular contexts. In this study, we aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 affects the development and progression of head and neck squamous cell carcinoma (HNSCC).MethodsThe biological functions of LINC00460 were assessed in several epithelial cancer cell lines. The subcellular localization of LINC00460 was evaluated by cell nuclear/cytoplasmic fractionation and fluorescence in situ hybridization. RNA pull-down assays, LS-MS/MS analysis, and RNA and chromatin immunoprecipitation assays were performed to identify the molecular mechanism by which LINC00460 promotes HNSCC progression. The clinical pathological features of LINC00460 and PRDX1 were evaluated in HNSCC tissues and paired adjacent normal tissues.ResultsLINC00460 enhanced HNSCC cell proliferation and metastasis in vitro and in vivo and induced epithelial–mesenchymal transition (EMT). LINC00460 primarily localized within the cytoplasm of HNSCC cells, physically interacted with PRDX1 and facilitated PRDX1 entry into the nucleus. PRDX1 promoted the transcription of LINC00460, forming a positive feedback loop. In addition, PRDX1 also promoted the transcription of EMT-related genes (such as ZEB1, ZEB2 and VIM) through enrichment on gene promoters in the nucleus. LINC00460 effectively induced HNSCC cell EMT in a PRDX1-dependent manner, and PRDX1 mainly mediated the EMT-promoting effect of LINC00460. High levels of LINC00460 and PRDX1 expression were positively associated with lymph metastasis, pathological differentiation and tumor size in HNSCC patients.ConclusionsLINC00460 promoted EMT in HNSCC cells by facilitating PRDX1 entry into the nucleus. LINC00460 and PRDX1 are promising candidate prognostic predictors and potential targets for cancer therapy for HNSCC.
Highlights
The Long noncoding RNA (lncRNA) LINC00460 plays crucial roles in several epithelial cancers, its mechanisms of action differ greatly in different cellular contexts
LINC00460 facilitated PRDX1 entry into the nucleus, and PRDX1 promoted the transcription of LINC00460 and epithelial– mesenchymal transition (EMT)-related genes PRDX1 knockdown significantly increased the levels of E-cadherin and decreased the levels of N-cadherin, Vimentin, Zinc-finger Ebox-binding homeobox 1 (ZEB1) and Zinc-finger E-box-binding homeobox 2 (ZEB2) in CAL-27 and HN30 cells, whereas the levels of E-cadherin were decreased and the levels of N-cadherin, Vimentin, ZEB1 and ZEB2 were increased in CAL-27 and HN30 cells stably transduced with PRDX1, as determined by Western blot analysis (Fig. 5a, b and Additional file 11: Figure S6A, B)
Compared with negative control (NC) group, overexpression of LINC00460 can effectively promote the enrichment of PRDX1 in promoter regions of ZEB1, ZEB2 and VIM genes (Fig. 5h). It showed that PRDX1 promoted the transcription of LINC00460 and EMT-related genes through enrichment in gene promoters in the nucleus
Summary
The lncRNA LINC00460 plays crucial roles in several epithelial cancers, its mechanisms of action differ greatly in different cellular contexts. We aimed to determine the potential clinical applications of LINC00460 and elucidate the mechanisms by which LINC00460 affects the development and progression of head and neck squamous cell carcinoma (HNSCC). Previous reports have shown that lncRNAs have complex and wide-ranging functions in the development of HNSCC, including functions associated with cancer growth, recurrence and metastasis [8], because of their irregular and specific expression patterns in HNSCC [9]. The emerging mechanisms of action of LINC00460 differ widely in different cellular contexts; the key effects and detailed molecular mechanisms of LINC00460 in HNSCC cells remain unclear and urgently need further study and investigation
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