Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer

Zhang, Lulin; Yao, Jun; Li, Wenyao; Zhang, Ce

doi:10.3727/096504017x14934840662335

Cited by 56 publications

(41 citation statements)

References 28 publications

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“…Upregulation of DOG1 in PC compared to normal pancreas was confirmed by qPCR for DOG1 mRNA. In contrast, it is well known that miR-21 is upregulated in CAFs in different types of human cancer, including breast and PC[ 45 - 48 ], which was also observed in this study. We found that miR-21 was predominantly expressed in j-CAFs compared to other FB/CAF subtypes.…”

Section: Discussionsupporting

confidence: 55%

Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

Nielsen¹,

Mortensen²,

Detlefsen³

2018

WJG

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AIMTo determine whether it is possible to identify different immune phenotypic subpopulations of cancer-associated fibroblasts (CAFs) in pancreatic cancer (PC).METHODSWe defined four different stromal compartments in surgical specimens with PC: The juxtatumoural, peripheral, lobular and septal stroma. Tissue microarrays were produced containing all pre-defined PC compartments, and the expression of 37 fibroblast (FB) and 8 extracellular matrix (ECM) markers was evaluated by immunohistochemistry, immunofluorescence (IF), double-IF, and/or in situ hybridization. The compartment-specific mean labelling score was determined for each marker using a four-tiered scoring system. DOG1 gene expression was examined by quantitative reverse transcription PCR (qPCR).RESULTSCD10, CD271, cytoglobin, DOG1, miR-21, nestin, and tenascin C exhibited significant differences in expression profiles between the juxtatumoural and peripheral compartments. The expression of CD10, cytoglobin, DOG1, nestin, and miR-21 was moderate/strong in juxtatumoural CAFs (j-CAFs) and barely perceptible/weak in peripheral CAFs (p-CAFs). The upregulation of DOG1 gene expression in PC compared to normal pancreas was verified by qPCR. Tenascin C expression was strong in the juxtatumoural ECM and barely perceptible/weak in the peripheral ECM. CD271 expression was barely perceptible in j-CAFs but moderate in the other compartments. Galectin-1 was stronger expressed in j-CAFs vs septal fibroblasts, PDGF-Rβ, tissue transglutaminase 2, and hyaluronic acid were stronger expressed in lobular fibroblasts vs p-CAFs, and plectin-1 was stronger expressed in j-CAFs vs l-FBs. The expression of the remaining 33 markers did not differ significantly when related to the quantity of CAFs/FBs or the amount of ECM in the respective compartments.CONCLUSIONDifferent immune phenotypic CAF subpopulations can be identified in PC, using markers such as cytoglobin, CD271, and miR-21. Future studies should determine whether CAF subpopulations have different functional properties.

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Section: Discussionsupporting

confidence: 55%

Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

Nielsen¹,

Mortensen²,

Detlefsen³

2018

WJG

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“…Wang et al (2016) [38] showed that miR-221 bound to the 3 -UTR of endothelial nitric oxide synthase traffic inducer (NOSTRIN) and inhibited its expression, and up-regulated miR-221 expression correlated with unsatisfactory survival in PDAC, and another study demonstrated that miR-221 is an oncogenic miRNA that contributes to Capan-2 cell proliferation by regulating the PTEN-Akt pathway [39]. In addition, miR-21 promotes epidermal growth factor (EGF)-induced proliferation, inhibits cell apoptosis, and accelerates cell cycle progression by targeting the PI3K/AKT and MAPK/ERK signaling pathways [40]; it is also associated with poor OS and disease-free survival in PDAC [41]. Frampton et al (2015) [42] identified three miRNAs (miR-21, miR-23a, and miR-27a) with high tumor expression, and the inhibition of miR-23a, miR-21, and miR-27a had promoting effects in decreasing the proliferation of PDAC cells in culture and the growth of xenograft tumors.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) is a class of the commonest malignant carcinomas. The present study aimed to elucidate the potential biomarker and prognostic targets in PDAC. The array data of GSE41368, GSE43795, GSE55643, and GSE41369 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRNAs) in PDAC were obtained by using GEO2R, and overlapped DEGs were acquired with Venn Diagrams. Functional enrichment analysis of overlapped DEGs and DEmiRNAs was conducted with Metascape and FunRich, respectively. The protein–protein interaction (PPI) network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) of DEmiRNAs and hub genes were investigated by Kaplan–Meier (KM) plotter (KM plotter). Transcriptional data and correlation analyses among hub genes were verified through GEPIA and Human Protein Atlas (HPA). Additionally, miRNA targets were searched using miRTarBase, then miRNA–DEG regulatory network was visualized with Cytoscape. A total of 32 DEmiRNAs and 150 overlapped DEGs were identified, and Metascape showed that DEGs were significantly enriched in cellular chemical homeostasis and pathways in cancer, while DEmiRNAs were mainly enriched in signal transduction and Glypican pathway. Moreover, seven hub genes with a high degree, namely, V-myc avian myelocytomatosis viral oncogene homolog (MYC), solute carrier family 2 member 1 (SLC2A1), PKM, plasminogen activator, urokinase (PLAU), peroxisome proliferator activated receptor γ (PPARG), MET proto-oncogene, receptor tyrosine kinase (MET), and integrin subunit α 3 (ITGA3), were identified and found to be up-regulated between PDAC and normal tissues. miR-135b, miR-221, miR-21, miR-27a, miR-199b-5p, miR-143, miR-196a, miR-655, miR-455-3p, miR-744 and hub genes predicted poor OS of PDAC. An integrative bioinformatics analysis identified several hub genes that may serve as potential biomarkers or targets for early diagnosis and precision target treatment of PDAC.

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“…Expression of miR-21 is up-regulated in various human tumor tissues and cells, such as brain glioma, ovarian cancer, bladder cancer, prostate cancer, lung cancer, breast cancer, thyroid cancer, esophageal cancer, liver cancer, bile duct cancer, pancreatic cancer, colorectal cancer, gastric cancer, and B cell lymphoma. miR-21 participates in the proliferation, migration, invasion, differentiation and apoptosis of tumor cells (26,27). In addition, miR-21 is involved in the regulation of multiple downstream target genes such as PTEN, PDCD4, RECK, and TIMP-3 (21,28).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

Zeng

et al. 2018

Exp Ther Med

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Abstract. The present study investigated the expression of microRNA (miR)-21 in non-small cell lung cancer (NSCLC) tissues, its biological functions and mechanism of autophagy regulation. A total of 46 patients with NSCLC were enrolled in the present study. To measure the expression of miR-21, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed. NSCLC A549 cells were transfected with miR-negative control (NC), miR-21 mimics or inhibitor. The CCK-8 assay was used to investigate the proliferation of A549 cells. To study migration and invasion abilities of A549 cells, The Transwell assay was performed. In addition, to determine the expression levels of ULK1, LC3B, AMPKα, p-AMPKα and p62 proteins, western blotting was conducted and laser confocal microscopy was performed to observe the formation of autophagosomes in A549 cells. To explore whether miR-21 regulates the biological functions of A549 cells via autophagy, an autophagy inhibitor, 3-MA, or agonist, rapamycin, were used in a rescue assay. Results indicated that miR-21 expression in NSCLC tissues was enhanced, and closely correlated with the occurrence and development of NSCLC. In vitro experiments showed that miR-21 mimics promoted the proliferation, migration and invasion of A549 cells, while miR-21 inhibitor inhibited these biological functions. Western blotting indicated that miR-21 upregulated autophagy marker LC3BⅡ protein, but downregulated p62 protein. Laser confocal microscopy showed that miR-21 activated autophagy of A549. Rescue experiments indicated that autophagy reversed the effect of miR-21 on the proliferation, migration and invasion of A549 cells. Western blotting data suggested that autophagy-related AMPK/ULK1 signaling pathway was activated by miR-21, and interference or overexpression of ULK1 reversed the biological functions of miR-21. The present study demonstrated that miR-21 expression in NSCLC tissues was upregulated and positively correlated with lymphatic metastasis and clinical staging. In addition, miR-21 regulated autophagy activity of NSCLC A549 cells via AMPK/ULK1 signaling pathway, and promoted the proliferation, migration and invasion of NSCLC A549 cells.

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Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated Drug Resistance in Pancreatic Cancer

Cited by 56 publications

References 28 publications

Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

Typing of pancreatic cancer-associated fibroblasts identifies different subpopulations

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

MicroRNA‑21 promotes the proliferation, migration and invasion of non‑small cell lung cancer A549 cells by regulating autophagy activity via AMPK/ULK1 signaling pathway

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