Table 1 Non-coding RNAs involved in endoplasmic reticulum stress pathway regulation
Non-coding RNAs | Mechanisms | Subjects | Study type | References |
|---|---|---|---|---|
LINP1 | LINP1 negatively regulates UPR pathways, particularly through interaction with eIF2α, preventing excessive UPR activation and contributing to cSCC development suppression | HSC-1, A43, and HaCaT cells Mice | In vitro and in vivo | [132] |
LUCRC | Knockdown of LUCRC in HCT116 cells results in differential regulation of genes. LUCRC positively regulates BIP expression, and its depletion led to altered splicing of XBP1 and reduced ATF6 processing in response to ER stress | HCT116 cells Human Mice | In vitro and in vivo | [133] |
GAS5 | In ARPE-19 cells exposed to high glucose (HG), upregulation of GAS5 results in a decrease in total protein expression levels of ATF4 and CHOP. Additionally, there is a reduction in the relative protein phosphorylation ratio of p-PERK/PERK and p-eIF2α/eIF2α compared to control groups | ARPE-19 cells | In vitro | [134] |
H19 | H19 is associated with a reduction in the expression of various proteins related to ER stress, including p-PERK, p-IRE1α, ATF6, CHOP, cleaved caspase-3, cleaved caspase-9, cleaved caspase-12, and BAX in cardiac tissues | HL-1 cells Mice | In vitro and in vivo | [135] |
MIR503HG | LncRNA MIR503HG has been found to act as a sponge for miR-224-5p, leading to the upregulation of TUSC3. This, in turn, results in the suppression of the ATF6 branch of the UPR and the development of gastric cancer | SGC7901 and BGC-823 Mice Human | In vitro and in vivo | Â |
miR-1291 | In silico predictions and experimental validation suggest that miR-1291 represses the expression of IRE1α mRNA | HuH7 cells | In vitro | [136] |
miR-424 | miR-424 appears to be intricately involved in the regulation of UPR by influencing the expression of ATF6, PERK signaling, and RIDD, with its downregulation being a part of the response to ER stress, mediated by PERK | MEFs, H9c2, and HEK 293T cells Mice | In vitro and in vivo | [137] |
miR-322 | The ER oxidoreductase PDIA6 and miR-322 are identified as key regulators of IRE1α activity. The reduction in ER Ca2+ levels and activation of store-operated Ca2+ entry led to decreased miR-322 abundance, subsequently stabilizing PDIA6 mRNA and amplifying IRE1α activity during ER stress | embryonic fibroblasts and COS-1 cells Mice | In vitro and in vivo | [56] |
miR-199a-5p | The research suggests that the protective impact of HUVEC-derived miR-199a-5p on neural cells occurs through exosome-mediated transfer, leading to the inhibition of ER stress-induced apoptosis and inflammation by targeting BIP | HUVECs, SH-SY5Y cells | In vitro | [138] |
miR-3184-5p | XBP1 has identified as a target gene for miR-3184-5p, and downstream molecular effects implicate the regulation of CD44, cyclin D1, MMP2, p65, p-AKT, p-STAT3, GRP78, IRE1, p-JNK, CHOP, caspase-12, and BCL-2 | HGC-27 cells Human | In vitro | [139] |
miR-30c-2-3p | The research demonstrates that miR-30c-2-3p inhibits the expression of XBP1, leading to a decrease in the ER folding capacity and an intensification of ER stress, as evidenced by Thioflavin T staining. The study further reveals that miR-30c-2-3p up-regulates pro-apoptotic proteins CHOP and BIM while down-regulating the ER stress response protein BIP/GRP78 | OVCAR3 (C430) and SKOV3 (C209) cells | In vitro | [140] |
miR-34c | Functional experiments demonstrate that overexpressing miR-34c or suppressing HMGB1 leads to inhibited cell proliferation, increased apoptosis, and induction of ER stress in NSCLC cells | MRC-5, A549, H460, H157, H1299, and H23 cells | In vitro | [141] |
miR-494 | The finding indicates that miR-494 negatively regulates ER stress in HUVECs. When miR-494 levels are increased (miR-494 mimic), there is a reduction in the expression of ER stress-responsive genes and proteins. Conversely, inhibiting miR-494 (miR-494 inhibitor) leads to an increase in the expression of ER stress-responsive genes | HUVECs cells | In vitro | [142] |
miR-665 | The data suggests that miR-665 targets the ER stress components XBP1 and ORMDL3. The predicted target sequence in the 3′-UTRs of these genes, along with experimental evidence supports the idea that miR-665 has a regulatory role in modulating the expression of XBP1 and ORMDL3 in the context of ER stress | Human | In vitro | [60] |
miR-204 | miR-204 has regulatory effects on ER stress markers in HTM cell lines. Without tunicamycin treatment, miR-204 alters the expression of GRP78/BIP and CHOP/DDIT3. Furthermore, in the presence of tunicamycin, miR-204 significantly inhibits the induction of ER stress markers (GRP94, GRP78/BIP, and CHOP/DDIT3) | HTM cells | In vitro | |
miR-1283 | The inhibition of miR-1283 appears to play a role in promoting ER stress through the regulation of the PERK/ATF4 pathway | CRL-1730 cells Mice | In vitro and in vivo | [144] |
miR-7112-3p | miR-7112-3p appears to play a crucial role in regulating the PERK-ATF4-CHOP-caspase 3/8 signaling pathway | CX-1 cells | In vitro | [145] |
miR-211 | Functional experiments involving antagomir and miR-211 expression have revealed a relationship between miR-211 expression and CHOP accumulation following ER stress. miR-211 has shown to regulate CHOP at both the protein and mRNA levels | NIH 3T3 cells Mice Human | In vitro | [146] |
miR-615-3p | miR-615-3p overexpression results in a significant decrease in CHOP protein levels under conditions of palmitate and tunicamycin treatment in both IRE-WT and Hepa 1–6 cells | Hepatoma cell line | In vitro | [147] |
miR-181 | Computational predictions suggested that miR-181 could target the 3′UTRs of three HSP70 family members. Experimental validation revealed a specific interaction between miR-181 and the 3′UTR of GRP78. This suggests that miR-181 may directly regulate GRP78 | Primary astrocyte | In vitro | [45] |
miR-378 | The provided experimental data suggests an intricate relationship between miR-378 and XBP1 during ER stress. The study employed MCF7 cells and observed that miR-378 undergoes downregulation in response to ER stress induced by Brefeldin A | MCF7, MDA-MB-231, and ZR-75-1 | In vitro | [148] |
miR-199a-5p and miR-495 | miR-199a-5p and miR-495 are suggested to interact with the 3′-UTR of GRP78, indicating a direct regulatory relationship | A459, QU-DB, HEK293T Human | In vitro | [149] |
miR-1202 | miR-1202-dependent inhibition of Rab1A is proposed to activate ER stress. Expression of GRP78, a marker of ER stress, significantly increases in cells transfected with miR-1202 vector. The protein expressions of Rab1A, Bcl-2, and Bax are altered in response to miR-1202, suggesting a potential link between miR-1202, Rab1A, ER stress, and apoptosis in glioma cells | U87, U251, U373, A172, and LN229 Human | In vitro | [150] |
miR-103/107 | The findings suggest that miR-103/107 plays a role in promoting ER stress-induced apoptosis in preadipocytes. The downregulation of miR-103/107 led to a reduction in ER stress markers, pro-apoptotic genes, and caspase-3 activity, indicating a protective effect against apoptosis in preadipocytes | Primary preadipocyte | In vitro | [151] |
miR-149 | In non-alcoholic fatty liver disease (NAFLD) mice, there is a notable increase in mRNA and protein expressions of GRP94 and Akt, indicating activation of the ATF6 pathway and ER stress. Transfection of miR-149 mimics into NAFLD mice led to a significant decrease in the expressions of GRP94 and Akt. This suggests that miR-149 inhibits the ATF6 signaling pathway and the expressions of its downstream proteins | Mice | In vitro and in vivo | [152] |
miR-185 | The overexpression of miR-185 attenuates ER stress-induced apoptosis in cardiomyocytes. This conclusion is supported by a reduction in the percentage of TUNEL-positive cardiomyocytes and changes in the protein levels of CHOP and cleaved-caspase 3 in response to increasing concentrations of miR-185 mimic | Cardiomyocytes | In silico and in vitro | [153] |
miR-221/222 | Downregulation of miR-221/222 protects HCC cells against ER stress-induced apoptosis. miR-221/222 mimics sensitize cells to apoptosis, while miR-221/222 inhibitors attenuate apoptosis, indicating a regulatory role for miR-221/222 in the apoptotic response to ER stress in HCC cells | HepG2 and SMMC-7721 | In vitro | [63] |
miR-520a | In Raji cells, miR-520a has found to significantly inhibit the expression of GRP78, GADD, p-PERK, and eIF2α. When Raji cells are treated with inhibitors of miR-520a, there is an observed increase in the expression levels of GRP78, GADD, p-PERK, and eIF2α | Raji cells | In vitro | [154] |