Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

Abstract

To survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic reticulum stress (ER stress) and triggers the unfolded protein response (UPR). UPR downstream components strictly control transcription and translation reprogramming to ensure selective gene expression, including that of non-coding RNA (ncRNAs), to adapt to adverse environments. NcRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating target gene expression and protein translation, and their aberrant expression is related to tumor development. Dysregulation of ncRNAs is involved in the regulation of various cellular characteristics of cancer cells, including growth, apoptosis, metastasis, angiogenesis, drug sensitivity, and tumor stem cell properties. Notably, ncRNAs and ER stress can regulate each other and collaborate to determine the fate of tumor cells. Therefore, investigating the interaction between ER stress and ncRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we summarize the ER stress-triggered UPR signaling pathways involved in carcinogenesis followed by the mutual regulation of ER stress and ncRNAs in cancer, which provide further insights into the understanding of tumorigenesis and therapeutic strategies.

On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm

“…Given the link between ER stress and metastasis (Urra et al, 2016;Cubillos-Ruiz et al, 2017;Chen and Cubillos-Ruiz, 2021), we tested if high ER stress could indeed drive migratory behavior (Nagelkerke et al, 2013;Feng et al, 2014;Urra et al, 2016;Zhao et al, 2020). Whereas CC14 and E3 cells treated with the classical ER-stress-inducer tunicamycin displayed enhanced levels of DDIT3 and HSPA5, as expected, they showed 3-fold reduced migration (Figure 6C; data not shown).…”

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

“…To survive, cancer cells trigger the unfolded protein response UPR. Non-coding RNAs (ncRNAs) play important roles in regulating protein translation and adaptation to adverse environments [ 119 ]. Mitochondria also are capable of exerting a UPR response (UPR mt).…”

HRC promotes anoikis resistance and metastasis by suppressing endoplasmic reticulum stress in hepatocellular carcinoma

“…The self-adaptation process when subjected to endoplasmic reticulum stress is named the unfolded protein response (UPR), which is to restore protein homeostasis 33 . The UPR has three transmembrane sensor protein pathways, including inositol-requiring enzyme 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6) pathways 34 . When the self-protection mechanism of UPR fails, the activation of ATF-CHOP can induce the apoptosis pathway 35 .…”