Cancer cells must overcome a variety of external and internal stresses to survive and
proliferate. These unfavorable conditions include the accumulation of mutations,
nutrient deficiency, oxidative stress, and hypoxia. These stresses can cause
aggregation of misfolded proteins inside the endoplasmic reticulum. Under these
conditions, the cell undergoes endoplasmic reticulum stress (ER‐stress), and
consequently initiates the unfolded protein response (UPR). Activation of the UPR
triggers transcription factors and regulatory factors, including long noncoding RNAs
(lncRNAs), which control the gene expression profile to maintain cellular stability and
hemostasis. Recent investigations have shown that cancer cells can ensure their
survival under adverse conditions by the UPR affecting the expression of lncRNAs.
Therefore, understanding the relationship between lncRNA expression and ER stress
could open new avenues, and suggest potential therapies to treat various types of
cancer.