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/

Zendy Plus

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

Zendy Tools

Zendy Open

Platinum‐based therapeutic strategies have been widely used in ovarian cancer treatment. However, drug resistance has greatly limited therapeutic efficacy. Recently, tolerance to cisplatin has been attributed to other factors unrelated to  DNA . p62 (also known as  SQSTM 1) functions as a multifunctional hub participating in tumorigenesis and may be a therapeutic target. Our previous study showed that p62 was overexpressed in drug‐resistant ovarian epithelial carcinoma and its inhibition increased the sensitivity to cisplatin. In this study, we demonstrate that the activity of the  NF ‐κB signaling pathway and K63‐linked ubiquitination of  RIP 1 was higher in cisplatin‐resistant ovarian ( SKOV 3/ DDP ) cells compared with parental cells. In addition, cisplatin resistance could be reversed by inhibiting the expression of p62 using si RNA . Furthermore, deletion of the  ZZ  domain of p62 that interacts with  RIP 1 in  SKOV 3 cells markedly decreased K63‐linked ubiquitination of  RIP 1 and inhibited the activation of the  NF ‐κB signaling pathway. Moreover, loss of the  ZZ  domain from p62 led to poor proliferative capacity and high levels of apoptosis in  SKOV 3 cells and made them more sensitive to cisplatin treatment. Collectively, we provide evidence that p62 is implicated in the activation of  NF ‐κB signaling that is partly dependent on  RIP 1. p62 promotes cell proliferation and inhibits apoptosis thus mediating drug resistance in ovarian cancer cells.

p62/ SQSTM 1 as an oncotarget mediates cisplatin resistance through activating RIP 1‐ NF ‐κB pathway in human ovarian cancer cells