The Role of miRNAs during Endoplasmic Reticulum Stress Induced Apoptosis in Digestive Cancer

Abstract

Digestive cancer is one of the leading causes of cancer mortality in the world. Despite a number of studies being conducted, the exact mechanism for treating digestive cancer has not yet been fully understood. To survive, digestive cancer cells are subjected to various internal and external adverse factors, such as hypoxia, nutritional deficiencies or drug toxicity, resulting in accumulation of misfolded and unfolded protein in endoplasmic reticulum (ER) lumen further leading to ER stress and the unfolded protein response (UPR). During the last years, studies on the relationship between ER stress and microRNAs (miRNAs) has burst on the scene. miRNAs are non-coding RNAs with a length of 21~22nucleotides involved in post-transcriptional regulation of gene expression, which could be regarded as oncomiRs (tumor inducers) and tumor suppressors regulating cancer cell proliferation, invasion, and apoptosis by differently affecting the expression of genes related to cancer cell signaling. Therefore, investigating the interaction between ER stress and miRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we mainly discuss miRNAs focusing on its regulation, role in ER stress induced apoptosis in Digestive cancer, expound the underlying mechanism, thus provides a theoretical foundation for finding new therapeutic targets of digestive cancer.

miR-140-3p enhances the sensitivity of LUAD cells to antitumor agents by targeting the ADAM10/Notch pathway

“…Wan et al, 2021 reported that miRNA-140-3p represses the proliferation of lung adenocarcinoma cells by targeting thymidylate synthetase [70]; Hu et al, 2022 also reported that miR-140-3p inhibits the progression of NSCLC by targeting Janus kinase 1 [71]. One miRNA may have multiple targets, so it plays a variety of physiological functions [72][73][74]. This makes the results of miR-140-3p targeting on other targets reported in these articles do not affect the finding that miR-140-3p can target on ADAM10 in this study.…”

Modulation of AKT Pathway-Targeting miRNAs for Cancer Cell Treatment with Natural Products

“…Several miRNAs control ER stress in digestive cancer with the involvement of FOXO ( Table 2 ) [ 1 ]. miR-132-3p is overexpressed in gastric cancers [ 130 ].…”

“…miRNAs are responsible for post-transcriptional gene regulation and are classified according to their oncogenic and tumor suppression functions in the regulation of diverse cell functions [ 1 ]. miRNAs are known to have several functions in the regulation of proliferation, apoptosis [ 2 ], autophagy [ 3 , 4 , 5 ], endoplasmic reticulum (ER) stress [ 1 , 6 ], ferroptosis [ 7 , 8 , 9 , 10 ], necroptosis [ 11 , 12 , 13 , 14 ], DNA damage response (DDR) [ 15 , 16 , 17 ], senescence [ 18 , 19 ], and migration [ 20 , 21 , 22 , 23 ] relating to cancer cells [ 23 , 24 , 25 ]. In the following, we briefly introduce the background for these cell functions and their relationships to miRNA.…”

“…In contrast, the effects of ER stress caused by tumor-suppressor miRNAs show the opposite function to that of oncogenic miRNAs [ 6 ]. Some miRNAs upregulate and downregulate ER stress in digestive cancer [ 1 ].…”

Advances in Molecular Pathology of Obstructive Sleep Apnea

“…Researchers indicate that the presence of endothelial dysfunction, atherosclerosis, and hypertension in OSA may be associated with up-regulations or down-regulations of some miRNAs [ 116 , 117 , 118 , 119 ]. Recent studies found that several miRNAs could influence IH process and affect hypoxia-induced cell apoptosis [ 120 ]. Some miRNAs up-regulated or down-regulated by hypoxia are direct targets of HIF-1α, HIF-2α, NF-κB, or their responsive genes, or some inflammatory signalings [ 121 , 122 , 123 , 124 ].…”