miR-30d, miR-181a and miR-199a-5p cooperatively suppress the endoplasmic reticulum chaperone and signaling regulator GRP78 in cancer

Sf, Su; Chang, Yi‐Wen; Andreu-Vieyra, Claudia; Jy, Fang; Yang, Zhiyao; Han, Bo; Lee, Amy; Liang, Gangning

doi:10.1038/onc.2012.483

Cited by 110 publications

(93 citation statements)

References 53 publications

(75 reference statements)

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“…It was reported that increased miR-181a aggravated injury in a mouse stroke model by inhibiting GRP78 protein expression levels, whereas reduced levels of miR-181a were associated with increased GRP78 protein levels and reduced injury (33). In several cancer cell lines, GRP78 was reported to be regulated by miR-199a-5p as well as miR-30d and miR-181a and cooperatively suppressed GRP78-mediated chemoresistance (45). Similarly, Dai et al (5) reported that miR-199a-5p was evaluated during hepatic ER stress and directly regulated the expression of GRP78 in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress

Jiang

Yun

Feng

et al. 2016

American Journal of Physiology-Cell Physiology

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lation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress. Am J Physiol Cell Physiol 310: C755-C763, 2016. First published February 10, 2016 doi:10.1152/ajpcell.00226.2015.-Endoplasmic reticulum (ER) stress has been linked to the pathogenesis of Parkinson's disease (PD). However, the role of microRNAs (miRNAs) in this process involved in PD remains poorly understood. Recent studies indicate that miR-384-5p plays an important role for cell survival in response to different insults, but the role of miR-384-5p in PD-associated neurotoxicity remains unknown. In this study, we investigated the role of miR-384-5p in an in vitro model of PD using dopaminergic SH-SY5Y cells treated with rotenone. We found that miR-384-5p was persistently induced by rotenone in neurons. Also, the inhibition of miR-384-5p significantly suppressed rotenone-induced neurotoxicity, while overexpression of miR-384-5p aggravated rotenone-induced neurotoxicity. Through bioinformatics and dual-luciferase reporter assay, miR-384-5p was found to directly target the 3=-untranslated region of glucose-regulated protein 78 (GRP78), the master regulator of ER stress sensors. Quantitative polymerase chain reaction and Western blotting analysis showed that miR-384-5p negatively regulated the expression of GRP78. Inhibition of miR-384-5p remarkably suppressed rotenone-evoked ER stress, which was evident by a reduction in the phosphorylation of activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1␣). The downstream target genes of ER stress including CCAAT/enhancer-binding protein-homologous protein (CHOP) and X box-binding protein-1 (XBP-1) were also decreased by the miR-384-5p inhibitor. In contrast, overexpression of miR-384-5p enhanced ER stress signaling. In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitors on cell apoptosis and ER stress signaling. Moreover, we observed a significant increase of miR-384-5p expression in primary neurons induced by rotenone. Taken together, our results suggest that miR-384-5p mediated ER stress by negatively regulating GRP78 and that miR-384-5p inhibition might be a novel and promising approach for the treatment of PD. endoplasmic reticulum stress; Parkinson's disease; miR-384-

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Section: Discussionmentioning

confidence: 99%

Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress

Jiang

Yun

Feng

et al. 2016

American Journal of Physiology-Cell Physiology

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“…However, the implications of upregulation of miR-181a in MPC samples remains unclear. Additionally, Su et al (36) reported that the downregulation of miR-30d and miR-181a in prostate tumors cooperatively suppresses the expression of glucose-regulated protein, 78 kDa (GRP78), a major endoplasmic reticulum chaperone and signaling regulator that is typically overexpressed in cancer (37). Differential expression of GRP78 was not observed in the present study; however, MYH11 was revealed to be another common target of miR-30d and miR-181a, indicating that miR-30d and miR-181a may cooperate to regulate the metastasis of PC cells.…”

Section: Discussionmentioning

confidence: 99%

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer

Guo

Zhu

et al. 2017

Oncol Lett

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Abstract. The present study aimed to identify the regulatory mechanisms associated with the metastasis of prostate cancer (PC). The microRNA (miRNA/miR) microarray dataset GSE21036 and gene transcript dataset GSE21034 were downloaded from the Gene Expression Omnibus database. Following pre-processing, differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between samples from patients with primary prostate cancer (PPC) and metastatic prostate cancer (MPC) with |log 2 fold change (FC)| >1 and a false discovery rate <0.05 were selected using the Linear Models for Microarray and RNA-seq Data 4 package of R. Next, a DEM-DEG regulatory network was constructed by downloading miRNA-DEG pairs from the miRNA.org database. Finally, functional annotation of each DEM-DEG module was performed using the Database for Annotation, Visualization and Integrated Discovery based on the Gene Ontology database. The upregulated miRNAs, including miR-144, miR-494 and miR-181a, exhibited a higher degree of connections compared with other nodes, including in the DEM-DEG regulatory network, and regulated a number of downregulated DEGs. According to the functional annotation of the DEM-DEG modules, miR-144 and its targeted DEGs enriched the highest number of biological process terms (36 terms), followed by miR-494 (24 terms), miR-30d (18 terms), miR-181a (15 terms), hsa-miR-196a (8 terms), miR-708 (7 terms) and miR-486-5p (2 terms). Therefore, these miRNAs may serve roles in the metastasis of PC cells via downregulation of their corresponding target DEGs.

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“…The potential links between the UPR, miR-1291, IRE1 and GPC3 require further clarification. BiP (GRP78), the major ER chaperone and signaling regulator, was shown to be a direct target of miR-30a, miR-181a and miR-199a-5p [78]. These three miRNAs are downregulated in prostate, colon and bladder tumors, and in a number of human cancer cell lines.…”

Section: Upr Mirnasmentioning

confidence: 99%

“…These three miRNAs are downregulated in prostate, colon and bladder tumors, and in a number of human cancer cell lines. Induction of these miRNAs in C42B prostate cancer cells attenuated BiP expression and induced apoptosis [78], meaning these miRNAs may be a part of the apoptotic UPR response. Another study by Dai et al [54] demonstrated that miR-199-5p is induced in hepatocytes during thapsigargin-induced ER stress, and targets BiP mRNA along with ATF6 and IRE1α.…”

Section: Upr Mirnasmentioning

confidence: 99%

Regulation of the unfolded protein response by microRNAs

Bartoszewska¹,

Kochan²,

Madanecki³

et al. 2013

Cellular and Molecular Biology Letters

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The unfolded protein response (UPR) is an adaptive response to the stress that is caused by an accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER). It is an important component of cellular homeostasis. During ER stress, the UPR increases the protein-folding capacity of the endoplasmic reticulum to relieve the stress. Failure to recover leads to apoptosis. Specific cellular mechanisms are required for the cellular recovery phase after UPR activation. Using bioinformatics tools, we identified a number of microRNAs that are predicted to decrease the mRNA expression levels for a number of critical components of the UPR. In this review, we discuss the potential role of microRNAs as key regulators of this pathway and describe how microRNAs may play an essential role in turning off the UPR after the stress has subsided.

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miR-30d, miR-181a and miR-199a-5p cooperatively suppress the endoplasmic reticulum chaperone and signaling regulator GRP78 in cancer

Cited by 110 publications

References 53 publications

Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress

Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress

Comparison of miRNA and gene expression profiles between metastatic and primary prostate cancer

Regulation of the unfolded protein response by microRNAs

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