Correction to: Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Liu A
PROVIDER: S-EPMC8638476 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Correction to: Antagonizing miR-455-3p inhibits chemoresistance and aggressiveness in esophageal squamous cell carcinoma.
Liu Aibin A Zhu Jinrong J Wu Geyan G Cao Lixue L Tan Zhanyao Z Zhang Shuxia S Jiang Lili L Wu Jueheng J Li Mengfeng M Song Libing L Li Jun J
Molecular cancer 20211201 1
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Project description:BackgroundThe plasticity of cancer stem cells (CSCs)/tumor-initiating cells (T-ICs) suggests that multiple CSC/T-IC subpopulations exist within a tumor and that multiple oncogenic pathways collaborate to maintain the CSC/T-IC state. Here, we aimed to identify potential therapeutic targets that concomitantly regulate multiple T-IC subpopulations and CSC/T-IC-associated pathways.MethodsA chemoresistant patient-derived xenograft (PDX) model of human esophageal squamous cell carcinoma (ESCC) was employed to identify microRNAs that contribute to ESCC aggressiveness. The oncogenic effects of microRNA-455-3p (miR-455-3p) on ESCC chemoresistance and tumorigenesis were examined by in vivo and in vitro chemoresistance, tumorsphere formation, side-population, and in vivo limiting dilution assays. The roles of miR-455-3p in activation of the Wnt/β-catenin and transforming growth factor-β (TGF-β)/Smad pathways were determined by luciferase and RNA immunoprecipitation assays.ResultsWe found that miR-455-3p played essential roles in ESCC chemoresistance and tumorigenesis. Treatment with a miR-455-3p antagomir dramatically chemosensitized ESCC cells and reduced the subpopulations of CD90+ and CD271+ T-ICs via deactivation of multiple stemness-associated pathways, including Wnt/β-catenin and TGF-β signaling. Importantly, miR-455-3p exhibited aberrant upregulation in various human cancer types, and was significantly associated with decreased overall survival of cancer patients.ConclusionsOur results demonstrate that miR-455-3p functions as an oncomiR in ESCC progression and may provide a potential therapeutic target to achieve better clinical outcomes in cancer patients.
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Project description:BackgroundBreast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.MethodsThe levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.ResultsHsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.ConclusionHsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.
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Project description:The aim of this work was to determine whether miR-455-3p regulates DNA methylation during chondrogenic differentiation of hMSCs. The expression of miR-455-3p and de novo methyltransferase DNMT3A was assessed in micromass culture of hBMSCs, which induced chondrogenic differentiation in vitro, and in E16.5 mice in vivo. A luciferase reporter assay was used to confirm whether miR-455-3p directly targets DNMT3A by interaction with the 3'-UTR. Using an Illumina Infinium Methylation EPIC microarray, genome-wide DNA methylation of hBMSCs with or without overexpressed miR-455-3p was examined for 28 days during induced chondrogenic differentiation. Here, we showed that miR-455-3p was more expressed during the middle stage of hBMSC chondrogenic differentiation, and less expressed in the late stage. DNMT3A was less expressed in the middle stage and more expressed in the late stage, and was also more expressed in the palms of miR-455-3p deletion mice compared to those of wild-type mice. The luciferase reporter assay demonstrated that miR-455-3p directly targets DNMT3A 3'-UTR. miR-455-3p overexpression inhibits the degenerate process during chondrogenic differentiation, while deletion of miR-455-3p in mice accelerated cartilage degeneration. Genome-wide DNA methylation analysis showed miR-455-3p overexpression regulates DNA methylation of cartilage-specific genes. GO analysis revealed PI3K-Akt signaling pathway was most hypomethylated. Our data show that miR-455-3p can regulate hMSC chondrogenic differentiation by affecting DNA methylation. Overexpression of miR-455-3p and DNA methylation inhibitors can thus potentially be utilized to optimize chondrogenic differentiation.
| S-EPMC5945650 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) leads to poor prognosis due to high aggressiveness and common chemoresistance. Dihydromyricetin (DMY), the main bioactive compound isolated from Ampelopsis grossedentata, exhibits broad anti-tumor effects. This study aimed to investigate the inhibitory effect of DMY on CCA tumor growth and epithelial-mesenchymal transition (EMT) and its underlying mechanism in CCA. DMY treatment significantly inhibited cell proliferation and EMT in CCA cell lines. The expression of ZEB1 and vimentin were down-regulated, while the level of E-cadherin was increased after DMY treatment. By analyzing the TCGA dataset, we found that miR-455 expression was significantly downregulated, while the level of ZEB1 was up-regulated in human CCA tumor tissues compared to normal samples. Mechanistic studies showed that ZEB1 was a direct target of miR-455-3p in CCA. Moreover, DMY treatment potently increased miR-455-3p expression and inhibited ZEB1 expression. Inhibition of miR-455-3p expression abolished DMY's inhibitory effects on tumor growth and EMT in both CCA cells and cell-engrafted nude mice. Finally, DMY significantly suppressed the expressions of p-PI3K and p-AKT, while silencing miR-455-3p remarkably abrogated the inhibitory effect. In conclusion, DMY suppresses tumor growth and EMT through regulating miR-455-3p in human cholangiocarcinoma, suggesting a potential option for CCA treatment.
| S-EPMC8425191 | biostudies-literature
Project description:BackgroundTo explore the role and mechanism of triptolide in regulating esophageal squamous cell carcinoma (ESCC) progression by mediating the circular RNA (circRNA)-related pathway.MethodsThe expression levels of circNOX4, miR-153-3p and special AT-rich sequence binding protein-1 (SATB1) were measured by qRT-PCR. Cell proliferation was confirmed by cell counting kit-8 assay and colony formation assay. Flow cytometry was employed to measure cell apoptosis and cell cycle process. Moreover, cell migration and invasion were detected using transwell assay. The protein levels of epithelial-mesenchymal transformation markers and SATB1 were determined by western blot analysis. Furthermore, dual-luciferase reporter assay and RIP assay were performed to confirm the interaction between miR-153-3p and circNOX4 or SATB1. Xenograft tumor models were built to verify the effects of triptolide and circNOX4 on ESCC tumor growth.ResultsCircNOX4 was highly expressed in ESCC tissues and cells, and its expression could be reduced by triptolide. Triptolide could inhibit ESCC proliferation, cell cycle process, migration, invasion, EMT process, and promote apoptosis, while these effects were reversed by circNOX4 overexpression. MiR-153-3p could be sponged by circNOX4, and the promotion effect of circNOX4 on the progression of triptolide-treated ESCC cells was abolished by miR-153-3p overexpression. SATB1 was a target of miR-153-3p. Also, SATB1 knockdown reversed the enhancing effect of miR-153-3p inhibitor on the progression of triptolide-treated ESCC cells. Triptolide reduced ESCC tumor growth by regulating the circNOX4/miR-153-3p/SATB1 axis.ConclusionTriptolide could hinder ESCC progression, which was mainly achieved by regulating the circNOX4/miR-153-3p/SATB1 axis.
| S-EPMC10912528 | biostudies-literature
Project description:Breast cancer is one of the most malignant diseases in women worldwide. Serum microRNAs (miRNAs), with the characteristics of high sensitivity and specificity, have recently attracted more attentions to serve as potential biomarkers for tumor diseases. In this study, 194 breast cancer patients' serum samples were collected before surgery and enrolled into different groups based on their diagnostic information. To search for breast cancer diagnostic biomarkers, serum miRNAs were screened by microarray in pooled samples of healthy volunteers and breast cancer patients in different clinical stages. The miRNAs were further verified in each individual patient's serum samples in diagnostic and predictive sets. The serum level of miR-1915-3p was upregulated and miR-455-3p was downregulated significantly in breast cancer patients compared with healthy volunteers. Furthermore, the patients with infiltrating carcinoma or lymph node metastasis had a higher serum level of miR-1915-3p and lower serum level of miR-455-3p than patients with the carcinoma in situ or patients without lymph node metastasis. ROC analysis suggested that miR-1915-3p and miR-455-3p had the potential as a promising serum diagnostic and predictive biomarkers of breast cancer. miR-1915-3p was over-expressed in certain human breast cancer cells. Functional experiments in vitro showed that miR-1915-3p enhanced cell proliferative and migrational abilities. Overexpression of miR-1915-3p repressed target gene DUSP3 and activated ERK1/2. Collectively, this study provided a new insight that miR-1915-3p might play a role in the development of breast cancer and that serum miR-1915-3p and miR-455-3p could serve as diagnostic and predictive biomarkers for breast cancer.
| S-EPMC6062026 | biostudies-literature
Project description:BackgroundGlobally, gastric cancer (GC) is one of the world's most widespread malignancies, with persistent high mortality and morbidity rates. Increasing evidence now suggests that microRNAs (miRNAs) participate in many biological processes, with miR-455-3p having key roles in the progression of diverse cancers. Nevertheless, miR-455-3p function and expression in GC remain unclear.MethodsWe explored miR-455-3p expression in GC using quantitative polymerase chain reaction (qPCR). To further examine the effect of miR-455-3p in GC, after transfecting miR-455-3p mimics or inhibitors into GC cells, 5-ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assays were performed to examine cell proliferation. Flow cytometry was used to detect apoptosis, and expression levels of Bax, Bcl-2, Snail, N-cadherin, E-cadherin, and Caspase-3 were assessed by western blotting (WB). Using online databases and luciferase assays, we identified armadillo repeat-containing protein 8 (ARMC8) as a promising target of miR-455-3p. A mouse tumor model was established to investigate actions of miR-455-3p in vivo. Expression levels of C-myc, cyclinD1, and β-catenin were examined using WB and immunofluorescence.ResultsMiR-455-3p expression was attenuated in GC tissue and cell lines. MiR-455-3p overexpression inhibited GC cell proliferation, epithelial-mesenchymal transition (EMT), as well as facilitated apoptosis, while suppression of miR-455-3p had the opposite effects. From luciferase assays, we confirmed that ARMC8 was a novel and direct downstream target gene of miR-455-3p, and that the tumor suppressive role of miR-455-3p was in part reversed due to ARMC8 overexpression. Moreover, miR-455-3p inhibited GC growth in vivo via ARMC8. We also observed that miR-455-3p repressed canonical Wnt pathway activation by binding to ARMC8.ConclusionsMiR-455-3p exerted tumor inhibitory effects in GC by targeting ARMC8. Therefore, intervening in the miR-455-3p/ARMC8/Wnt/βcatenin axis could be a promising novel treatment strategy for GC.
| S-EPMC10318695 | biostudies-literature
Project description:ObjectiveWith the number of patients with acute pancreatitis (AP) increasing year by year, it is pressing to explore new key genes and markers for the treatment of AP. miR-455-3p/solute carrier family 2 member 1 (Slc2a1) obtained through bioinformatics analysis may participate in the progression of AP.Materials and methodsThe C57BL/6 mouse model of AP was constructed for subsequent studies. Through bioinformatics analysis, the differentially expressed genes related to AP were screened and hub genes were identified. A caerulein-induced AP animal model was constructed to detect the pathological changes of mouse pancreas by HE staining. The concentrations of amylase and lipase were measured. Primary mouse pancreatic acinar cells were isolated and subjected to microscopy to observe their morphology. The enzymatic activities of trypsin and amylase were detected. The secretion of inflammatory cytokines in mouse were measured with the ELISA kits of TNF-α, IL-6 and IL-1β to determine pancreatic acinar cell damage. A binding site between the Slc2a1 3' UTR region and the miR-455-3p sequence was verified by dual-luciferase reporter assay. The expression of miR-455-3p was quantified by qRT-PCR, and Slc2a1 were detected by western blot.ResultsA total of five (Fyn, Gadd45a, Sdc1, Slc2a1, and Src) were identified by bioinformatics analysis, and miR-455-3p/Slc2a1 were further studied. HE staining results showed that the AP models were successfully established by caerulein induction. In mice with AP, the expression of miR-455-3p was reduced, while that of Slc2a1 was increased. In the caerulein-induced cell model, the expression of Slc2a1 was significantly reduced after intervention of miR-455-3p mimics, whereas increased after miR-455-3p inhibitor treatment. miR-455-3p decreased the secretion of inflammatory cytokines in the cell supernatant, reduced the activity of trypsin and amylase, and alleviated the cell damage induced by caerulein. In addition, Slc2a1 3'UTR region was bound by miR-455-3p, and its protein expression was also regulated.ConclusionmiR-455-3p alleviated caerulein-induced mouse pancreatic acinar cell damage by regulating the expression of Slc2a1.
| S-EPMC10317017 | biostudies-literature
Project description:MicroRNAs are involved in tumor initiation and progression by regulating oncogenes and tumor suppressor genes. Here we found that miR-495 are lower in clinical ESCC tissues than in adjacent non-tumor tissues. Moreover, the lower miR-495 expression correlated with increased lymph node metastasis (LNM), invasion and TNM stage. miR-495 overexpression predicted a favorable outcome in ESCC patients. miR-495 targeted a site in the 3'-UTR of Akt1, and miR-495 levels correlated inversely with Akt1 protein levels in ESCC tissue samples. Overexpression of miR-495 suppressed cell proliferation, blocked G1/S phase transition, and decreased migration and invasion by two ESCC cell lines in vitro and in vivo. Restoration of Akt1 protein levels in miR-495-overexpressing ESCC cells attenuated the inhibitory effects of miR-495. In addition, miR-495 suppressed cell cycle transition and the EMT signaling pathway through targeting Akt1, thereby inhibiting ESCC cell proliferation, migration, and invasion. Our results suggest that miR-495 may act as a tumor suppressor by targeting Akt1 in ESCC.
| S-EPMC5239471 | biostudies-literature
Project description:BackgroundExosomal miRNAs have emerged as promising biomarkers for cancer. However, little is known about the role of exosomal miRNAs in the response prediction of esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy (CRT).MethodsIn this prospective study, 40 ESCC patients treated by CRT were enrolled from January 2021 to June 2022. Exosomes were isolated from plasma through EXODUS platform. We used small RNA sequencing in 14 samples of ESCC patients (7 responders, 7 non-responders) and the selected exosomal miRNAs were further validated in the extended cohort of 40 ESCC patients by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsIn the discovery phase, we identified five significantly differentially expressed exosomal miRNAs from miRNA sequencing data between the responder and non-responder patients. In the extended groups of responders (n = 27) and non-responders (n = 13), only miR-23b-3p (p = 0.035, AUC = 0.708) and miR-25-3p (p < 0.001, AUC = 0.932) were confirmed to have the predictive ability to distinguish non-responders from responders. The patients with low levels of miR-25-3p had a significantly shorter progression-free survival (PFS) than those with high levels (p = 0.035). Multivariate Cox regression analysis revealed that miR-25-3p may serve as an independent predictive biomarker of PFS in ESCC patients received CRT.ConclusionExosomal miR-25-3p and miR-23b-3p serve as promising biomarkers for predicting the early effectiveness of CRT in locally advanced ESCC patients, whereas miR-25-3p is a novel prognostic marker for ESCC. However, further larger prospective studies are needed to confirm their utility for individualized treatment decision in ESCC.
| S-EPMC11465297 | biostudies-literature