The lincRNA JUNI regulates the stress-dependent induction of c-Jun, cellular migration and survival through the modulation of the DUSP14-JNK axis

Vikash Kumar, Xavier Sabaté-Cadenas, Isha Soni, Esther Stern, Carine Vias, Doron Ginsberg, Carlos Romá-Mateo, Rafael Pulido, Martin Dodel, Faraz K. Mardakheh, Alena Shkumatava, Eitan Shaulian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer cells employ adaptive mechanisms to survive various stressors, including genotoxic drugs. Understanding the factors promoting survival is crucial for developing effective treatments. In this study, we unveil a previously unexplored long non-coding RNA, JUNI (JUN-DT, LINC01135), which is upregulated by genotoxic drugs through the activation of stress-activated MAPKs, JNK, and p38 and consequently exerts positive control over the expression of its adjacent gene product c-Jun, a well-known oncoprotein, which transduces signals to multiple transcriptional outputs. JUNI regulates cellular migration and has a crucial role in conferring cellular resistance to chemotherapeutic drugs or UV radiation. Depletion of JUNI markedly increases the sensitivity of cultured cells and spheroids to chemotherapeutic agents. We identified 57 proteins interacting with JUNI. The activity of one of them the MAPK phosphatase and inhibitor, DUSP14, is counteracted by JUNI, thereby, facilitating efficient JNK phosphorylation and c-Jun induction when cells are exposed to UV radiation. The antagonistic interplay with DUSP14 contributes not only to c-Jun induction but also augments the survival of UV-exposed cells. In summary, we introduce JUNI as a novel stress-inducible regulator of c-Jun, positioning it as a potential target for enhancing the sensitivity of cancer cells to chemotherapy.

Original languageAmerican English
Pages (from-to)1608-1619
Number of pages12
JournalOncogene
Volume43
Issue number21
DOIs
StatePublished - 21 May 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Fingerprint

Dive into the research topics of 'The lincRNA JUNI regulates the stress-dependent induction of c-Jun, cellular migration and survival through the modulation of the DUSP14-JNK axis'. Together they form a unique fingerprint.

Cite this