The expression of miRNA-152-3p and miRNA-185 in tumor tissues versus margin tissues of patients with chemo-treated breast cancer.
Ontology highlight
ABSTRACT: Objective
Breast cancer (BC) is the most significant and lethal type of cancer in women. Although there are many newly develop chemotherapy drugs for patients with BC treating at various stages, drug resistance is the most important obstacle in their effectiveness for BC treatment. On the other hand, microRNAs are considered key regulators of genes involved in carcinogenesis and chemoresistance in cancers. The purpose of this study was to evaluate the role of miR-152-3p and miR-185 in intrinsic chemoresistance and proliferation of BC. In addition, the potential role of these miRNAs during chemoresistance was evaluated through possible signaling pathways.Results
Here, miR-152-3p was significantly downregulated in tumor tissues compared to the corresponding margin tissues in patients with BC (p-value ≥ 0.04407 and fold change = - 2.0552). In contrast, no statistically significant difference was observed in the miR-185 expression between the two groups. Furthermore, no significant correlation was found between the expression of these two miRNAs and subfactors, including cancer family history, abortion, and age. Downregulation of miR-152-3p could be considered a promising regulator of BC chemoresistance.
SUBMITTER: Safi A
PROVIDER: S-EPMC8207775 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Increasing evidence shows that liver tumor-initiating cells (T-ICs) closely associated with the progression, metastasis, recurrence and chemo-resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. Here we show that miR-361-3p is upregulated in liver T-ICs. Knockdown of miR-361-3p impairs the self-renewal and tumorigenicity liver T-ICs. Conversely, forced miR-361-3p expression enhances the self-renewal and tumorigenicity liver T-ICs. Mechanistically, miR-361-3p directly targets SOX1 via binding its 3'-UTR in liver T-ICs. Moreover, miR-361-3p knockdown hepatoma cells are more sensitive to cisplatin or sorafenib treatment. Clinical cohort analysis demonstrates that miR-361-3p low HCC patients are benefited from TACE (transcatheter arterial chemoembolization) or sorafenib treatment. In conclusion, our findings revealed the crucial role of the miR-361-3p in liver T-IC expansion and TACE or sorafenib response, rendering miR-361-3p an optimal target for the prevention and intervention in HCC.
| S-EPMC7847642 | biostudies-literature
Project description:The expression of the c-myc oncogene at both protein and mRNA levels is transient and begins to be turned off 3-6 h after growth stimulation of cultured cells. The exact mechanism(s) underlying this down-regulation of c-Myc remains incompletely understood. Here we report the identification of miR-185-3p as a novel feedback regulator of c-Myc. This microRNA (miRNA) was initially identified as one of the c-Myc target miRNA transcripts through analysis of RNA samples isolated from cells prior to and after serum stimulation and further verified by real-time PCR, luciferase reporter, and ChIP assays. Interestingly, overexpression of wild type, but not mutant, miR-185-3p decreased the protein, but not mRNA, level of c-Myc in a dose-dependent fashion and also drastically abated the serum induction of c-Myc level in human cancer cells by targeting the coding sequence of c-Myc mRNA, consequently suppressing c-Myc-mediated proliferation. A miR-185-3p inhibitor rescued the inhibition of c-Myc expression by endogenous miR-185-3p. Thus, our results unveil miR-185-3p as the first miRNA that monitors c-Myc levels via an autoregulatory feedback mechanism in response to serum stimulation.
| S-EPMC3190790 | biostudies-literature
Project description:Tumor-associated macrophages (TAMs) play a central role in tumor progression, metastasis, and recurrence after treatment. Macrophage plasticity and diversity allow their classification along a M1-M2 polarization axis. Tumor-associated macrophages usually display a M2-like phenotype, associated with pro-tumoral features whereas M1 macrophages exert antitumor functions. Targeting the reprogramming of TAMs toward M1-like macrophages would thus be an efficient way to promote tumor regression. This can be achieved through therapies including chemotherapy, immunotherapy, and radiotherapy (RT). In this review, we first describe how chemo- and immunotherapies can target TAMs and, second, we detail how RT modifies macrophage phenotype and present the molecular pathways that may be involved. The identification of irradiation dose inducing macrophage reprogramming and of the underlying mechanisms could lead to the design of novel therapeutic strategies and improve synergy in combined treatments.
| S-EPMC5509958 | biostudies-other
Project description:BackgroundTreating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear.MethodsComputational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo)).ResultsThe in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated.ConclusionExosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.
| S-EPMC8315867 | biostudies-literature
Project description:Increasing evidence suggests that global downregulation of miRNA expression is a hallmark of human cancer, potentially due to defects in the miRNA processing machinery. In this study, we found that the protein expression of Argonaute 2 (AGO2), a key regulator of miRNA processing, was downregulated in colorectal cancer (CRC) tissues, which was also consistent with the findings of the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Furthermore, the correlation between the levels of AGO2 and epithelial-mesenchymal transition (EMT) markers (E-cadherin and vimentin) indicated that reduced levels of AGO2 promoted EMT in CRC. Low expression of AGO2 was an indicator of a poor prognosis among CRC patients. Knockdown of AGO2 in CRC cells promoted migration, invasion and metastasis formation in vitro and in vivo but had no influence on proliferation. To provide detailed insight into the regulatory roles of AGO2, we performed integrated transcriptomic, quantitative proteomic and microRNA sequencing (miRNA-seq) analyses of AGO2 knockdown cells and the corresponding wild-type cells and identified neuropilin 1 (NRP1) as a new substrate of AGO2 via miR-185-3p. Our data provided evidence that knockdown of AGO2 resulted in a reduction of miR-185-3p expression, leading to the upregulation of the expression of NRP1, which is a direct target of miR-185-3p, and elevated CRC cell metastatic capacity. Inhibition of NRP1 or treatment with a miR-185-3p mimic successfully rescued the phenotypes of impaired AGO2, which suggested that therapeutically targeting the AGO2/miR-185-3p/NRP1 axis may be a potential treatment approach for CRC.
| S-EPMC8042018 | biostudies-literature
Project description:BackgroundMiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer.MethodsFifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed.ResultsBoth miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs.ConclusionsThere was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.
| S-EPMC5580437 | biostudies-literature
Project description:The purpose of the present study was to examine the epigenetic mechanism by which microRNA (miR)-152-3p regulates proliferation in non-small cell lung cancer A549 cells via neural cell adhesion molecule 1 (NCAM1). Bisulfite sequencing PCR (BSP), the gold standard for methylation detection, uses bisulfite-treated DNA to determine its pattern of methylation. Treatment of DNA with bisulfite converts cytosine residues to uracil, but leaves 5-methylcytosine residues unaffected. It was conducted and demonstrated a relatively high level of methylation in the miR-152-3p promoter region. Chromatin immunoprecipitation was combined with PCR to detect the binding of DNA methyltransferase 3B (DNMT3B) protein to miR-152-3p, which tends to occur in the core region of the miR-152-3p gene in A549 cells. Luciferase assay identified NCAM1 as the target gene of miR-152-3p. MTT, colony formation and Transwell assays indicated that miR-152-3p could decrease cell proliferation and invasion and in addition to reducing the expression level of NCAM1. Overexpression of NCAM1 could attenuate the effect of miR-152-3p. DNMT3B knockdown decreased the proliferative ability of A549 cells and increased the expression of miR-152-3p, while decreased that of NCAM1. After treatment with miR-152-3p inhibitor, these effects were attenuated and the NCAM1 expression level was upregulated. The results indicated that miR-152-3p may suppress the proliferation of A549 cells by downregulating NCAM1. In addition, DNMT3B negatively regulated the expression of miR-152-3p via modulation of the methylation level in the miR-152-3p core region, thus mediating the proliferation of lung tumor cells.
| S-EPMC8607351 | biostudies-literature
Project description:Background: Hepatic fibrosis (HF) is characterized by activation of hepatic stellate cells (HSCs) and extensive deposition of extracellular matrix components, especially collagens. However, effective antifibrotic therapies are still lacking. Recently, circular RNAs (circRNAs) have been identified as novel regulators of HF. Methods: circRNAs profile was screened by RNA sequencing and the location of circ_0008494 was confirmed by fluorescence in situ hybridization assay in human HF tissues. Bioinformatics analysis was used for result prediction and dual-luciferase reporter, together with AGO-RIP and biotin-coupled miRNA capture assays, were used to determine miR-185-3p/collagen type I alpha 1 chain (Col1a1) as the target of circ_0008494. A stable circ_0008494-interfering human HSCs cell line was constructed and used to determine the regulatory mechanism of circ_0008494/miR-185-3p/Col1a1 axis. Results: circ_0008494 was abundantly and significantly over-expressed in human HF tissues and located at the cytoplasm of HSCs. Together, dual-luciferase reporter, AGO-RIP and biotin-coupled miRNA capture assays confirmed that circ_0008494 acted as a sponge of miR-185-3p. Cell functional experiments and rescue assays demonstrated suppressing circ_0008494 could inhibit activation, proliferation, migration of HSCs and promote their apoptosis through miR-185-3p. In particular, the HF indicator, Col1a1, was validated as the direct target of miR-185-3p and the suppression of circ_0008494 inhibited the expression of Col1a1 by releasing miR-185-3p. Conclusion: Knocking down circ_0008494 inhibited HSCs activation through the miR-185-3p/Col1a1 axis. circ_0008494 could be a promising treatment target for HF.
| S-EPMC9713816 | biostudies-literature
Project description:MicroRNA-185 (miR-185) is down-regulated in various tumor types. However, the cytological mechanism for inhibiting and restraining tumor growth of non-small-cell carcinoma (NSCLC) remains to be elucidated. In this study, it was revealed that miR-185 is significantly down-regulated in both NSCLC tumor tissues and cell lines, and over-expression of miR-185 inhibited cell growth, migration and invasion. To investigate the cellular machinery involved in miR-185's regulation of tumor growth, it was found that miR-185 directly targets SRY-Box 13 (SOX13). In addition, miR-185 regulated cell proliferation, migration, invasion and increased chemo-sensitivity in H1975 cells by inhibiting SOX13. MiR-185 also inhibited tumor growth and suppressed SOX13 in nude mouse xenograft tumors. To investigate the clinical relevance of these consequences, 24 pairs of NSCLC tissues and adjacent normal tissues were collected to determine expression of miR-185 and SOX13. It was demonstrated that miR-185 levels are significantly and inversely correlated with SOX13 levels in these NSCLC tissues, suggesting that these findings have implications for translational application with respect to NSCLC diagnostics and therapy.
| S-EPMC6129524 | biostudies-literature
Project description:For a long time, the BARD1 (BRCA1-associated RING domain 1) protein has been considered as a BRCA1 (BReast Cancer susceptibility gene 1, early onset) interactor, and tumor suppressor mutated in breast and ovarian cancers. Despite its functions in a stable heterodimer with BRCA1, there is increasing evidence for BRCA1-independent functions of BARD1. Here, we investigated BARD1 expression and function in human acute myeloid leukemias and their modulation by epigenetic mechanisms and microRNA. We show that the HDACi (histone deacetylase inhibitor) Vorinostat reduces BARD1 mRNA levels by increasing miR-19a and miR-19b expression levels. Moreover, we identify specific BARD1 isoforms that might act as tumor diagnostic and prognostic markers. Two-condition experiment: untreated NB4 cells (control) vs. NB4 cells treated with 5µM SAHA (Vorinostat) for 6h. Biological replicates: 3 control, 3 treated, independently grown and harvested at 6 hours. One replicate per array.
| S-ECPF-GEOD-37374 | biostudies-other