English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Background  Long intergenic noncoding RNA p21 (lincRNA-p21) is considered a target of wild-type p53, but little is known about its regulation by mutant p53 and its functions during the progression of head and neck squamous cell carcinoma (HNSCC).    Methods  RNAscope was used to detect the expression and distribution of lincRNA-p21. Chromatin immunoprecipitation and electrophoretic mobility shift assays were performed to analyze the transcriptional regulation of lincRNA-p21 in HNSCC cells. The biological functions of lincRNA-p21 were investigated in vitro and in vivo. RNA immunoprecipitation and pull-down assays were used to detect the direct binding of lincRNA-p21.    Results  Lower lincRNA-p21 expression was observed in HNSCC tissues and indicated worse prognosis. Both wild and mutant type p53 transcriptionally regulated lincRNA-p21, but nuclear transcription factor Y subunit alpha (NF-YA) was essential for mutant p53 in the regulation of lincRNA-p21. Ectopic expression of lincRNA-p21 significantly inhibited cell proliferation capacity in vitro and in vivo and vice versa. Moreover, the overexpression of lincRNA-p21 induced G1 arrest and apoptosis. Knockdown NF-YA expression reversed tumor suppressor activation of lincRNA-p21 in mutant p53 cells, not wild-type p53 cells. A negative correlation was observed between lincRNA-p21 and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in HNSCC tissues. High lincRNA-p21 expression inhibited Janus kinase 2 (JAK2)/STAT3 signal activation and vice versa. Further, we observed direct binding to STAT3 by lincRNA-p21 in HNSCC cells, which suppressed STAT3-induced oncogenic potential.    Conclusions  Our results revealed the transcriptional regulation of lincRNA-p21 by the mutant p53/NF-YA complex in HNSCC. LincRNA-p21 acted as a tumor suppressor in HNSCC progression, which was attributed to direct binding to STAT3 and blocking of JAK2/STAT3 signaling.    Electronic supplementary material  The online version of this article (10.1186/s12943-019-0993-3) contains supplementary material, which is available to authorized users.

p53-targeted lincRNA-p21 acts as a tumor suppressor by inhibiting JAK2/STAT3 signaling pathways in head and neck squamous cell carcinoma