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 Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear.    Methods  The autophagy-suppressive circRNA  circPARD3  was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect  circPARD3  expression and subcellular localization. Biological functions of  circPARD3  were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of  circPARD3  was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining.    Results  Autophagy was inhibited in LSCC, and  circPARD3  was upregulated in the LSCC tissues ( n  = 100,  p  < 0.001). High  circPARD3  level was associated with advanced T stages ( p  < 0.05), N stages ( p  = 0.001), clinical stages ( p  < 0.001), poor differentiation degree ( p  = 0.025), and poor prognosis ( p  = 0.002) of LSCC patients ( n  = 100). Functionally,  circPARD3  inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging  miR-145-5p  was the main mechanism of  circPARD3  inhibited autophagy, promoting LSCC progression and chemoresistance.    Conclusion  Our study reveals that the novel autophagy-suppressive  circPARD3  promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment.    Graphical abstractSupplementary Information  The online version contains supplementary material available at 10.1186/s12943-020-01279-2.

molecular cancer

circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway