Biology subjects

Stern, E.

Publications and source records attributed to Stern, E..

3 recordsLinked to original sources

bioRxiv2023

The stress-induced lincRNA JUNI is a critical factor for cancer cell survival whose interactome is a prognostic signature in clear cell renal cell carcinoma

Cancer cells rely on adaptive mechanisms to survive the multiple stressors they encounter, including replication stress, toxic metabolic products and exposure to genotoxic drugs. Understanding the factors involved in these stress responses is crucial for developing effective treatments. Here, we describe a previously unstudied long non-coding RNA (lncRNA), JUNI (JUN-DT, LINC01135), which is regulated by MAPK and responsive to stress. JUNI positively regulates the expression of its neighboring gene JUN, a key transducer of signals that regulate multiple transcriptional outputs. Our findings reveal that silencing JUNI sensitizes cancer cells to chemotherapeutic drugs or UV radiation, and that its prolonged silencing leads to cell death regardless of stress exposure, highlighting the pro-survival importance of JUNI. We identified 57 proteins that interact with JUNI and found that the activity of one of them, the MAPK phosphatase and inhibitor DUSP14, is inhibited by JUNI. This effect results in c-Jun induction following exposure of cancer cells to UV radiation and promotes cellular survival. Although JUNI regulates c-Jun and its downstream targets, the pro-survival effects in cells not exposed to stress are only partially dependent on c-Jun regulation. JUNI expression levels significantly correlate with patients survival across 11 different types of cancer. Interestingly, the correlation of DUSP14 expression levels with patients survival in nine of these tumors is coherently inverse, indicating contradicting effects that are relevant not only for c-Jun induction and cellular survival but also in human cancer. Notably, we observed particularly significant antagonistic correlations in clear cell renal cell carcinoma (ccRCC) (p=5.7E-05 for JUNI and p=2.9E- 05 for Dusp14). In fact, the expression levels of 76% of JUNI-interacting proteins predict the prognosis of ccRCC patients significantly. Furthermore, a combined hazard ratio calculation demonstrates that this gene combination serves as a highly specific prognostic signature for ccRCC. Overall, our findings reveal a new important factor in stress signaling and cellular survival that is involved in ccRCC.

cell biology↗

bioRxiv2023

Perception of near-threshold visual stimuli is influenced by pre-stimulus alpha-band amplitude but not by alpha phase

Ongoing brain activity preceding visual stimulation has been suggested to shape conscious perception. The underlying mechanisms are still under debate, although alpha oscillations have been pointed out as the main explanatory candidate. According to the pulsed-inhibition framework, bouts of functional inhibition arise in each alpha cycle, allowing information to be processed in a pulsatile manner. Consequently, it has been hypothesized that perceptual outcome can be influenced by the specific phase of alpha oscillations prior to the stimulus onset, although empirical findings are controversial. In this study, we aimed to shed light on the role of pre-stimulus alpha oscillations in visual perception. To this end, we recorded electroencephalographic (EEG) activity while participants performed three near-threshold visual detection tasks with different attentional involvement: a no-cue task, a non-informative cue task (50% cue validity), and an informative cue task (100% cue validity). Cluster-based permutation statistics were complemented with Bayesian analyses to test the effect of pre-stimulus oscillatory amplitude and phase on visual awareness. We additionally examined whether these effects differed on trials with low and high oscillatory amplitude, as expected from the pulsed-inhibition theory. Our results show a clear effect of pre-stimulus alpha amplitude on conscious perception, but only when alpha fluctuated spontaneously and was not modulated by attention, supporting the notion that alpha-band power indexes neural excitability. In contrast, we did not find any evidence that pre-stimulus alpha phase influences the perceptual outcome, not even when differentiating between low and high amplitude trials. Furthermore, Bayesian analysis provided moderate evidence in favor of the absence of phase effects. Taken together, our results challenge the central theoretical predictions of the pulsed-inhibition framework, at least for the particular experimental conditions used here.

neuroscience↗

bioRxiv2022

Cancer cells survival is dependent on the lincRNA JUNI

Identification of key factors for cellular survival is a basis for therapy. We identified JUNI (linc01135) as a stress-regulated lncRNA, essential for cell survival and implicated in cancer. Besides regulating c-Jun expression we demonstrate c-Jun-independent, robust requirement for cell survival. Analysis of median survival of cancer patients suffering from various types of cancer reveals correlations of JUNI expression levels with alterations in patients survival. JUNIs antagonistic interaction with DUSP14, a negative regulator of the JNK pathway, underlies the regulation of c-Jun and partial effects on cellular survival. Consistently, DUSP14 expression is coherently inversely-correlated with the survival of patients suffering from the same types of cancer. Our data suggests that JUNI is a novel master regulator of cell fate. SummaryJUNI is a novel regulator of cell survival, JNK activation and c-Jun expression, implicated in survival of cancer patients

cell biology↗