Dataset Information

Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.

ABSTRACT: Background:5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Methods:Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay. Results:In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the pro-apoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model. Conclusion:We found that the downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.

SUBMITTER: Wang W

PROVIDER: S-EPMC7047986 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.

Wang Wei W Liu Bowei B Sun Suofeng S Lan Ling L Chen Yu Y Han Shuangyin S Li Xiuling X Li Zhaoshen Z

OncoTargets and therapy 20200224

<h4>Background</h4>5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells.<h4>Methods</h4>Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect ...[more]

PMID: 32158231

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Project description:BACKGROUND:MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease. OBJECTIVE:The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages. DESIGN:A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis. SETTING:Genome-wide microRNA expression profiling was performed. PATIENTS:A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included. MAIN OUTCOME MEASURES:MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor. RESULTS:A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01). LIMITATIONS:Our microRNA profile was generated in a small subset of patients and will require validation in more samples. CONCLUSIONS:We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.

Project description:Abnormal expression of microRNA (miR) is associated with the occurrence and progression of various types of cancers, including papillary thyroid carcinoma (PTC). In the present study, the aim was to explore miR?486?5p expression and its role in PTC, as well as to investigate the biological function of its potential target genes. The expression levels of miR?486?5p and its clinicopathological significance were examined in 507 PTC and 59 normal thyroid samples via The Cancer Genome Atlas (TCGA). Subsequently, the results were validated using data from Gene Expression Omnibus (GEO) and ArrayExpress. Receiver operating characteristic and summary receiver operating characteristic curves were used to assess the ability of miR?486?5p in distinguishing PTC from normal tissue. Furthermore, potential miR?486?5p mRNA targets were identified using 12 prediction tools and enrichment analysis was performed on the encoding genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The expression levels of miR?486?5p were consistently downregulated in PTC compared with in normal tissue across datasets from TCGA, GEO (GSE40807, GSE62054 and GSE73182) and ArrayExpress (E?MTAB?736). The results also demonstrated that miR?486?5p expression was associated with cancer stage (P=0.003), pathologic lymph node (P=0.047), metastasis (P=0.042), neoplasm (P=0.012) and recurrence (P=0.016) in patients with PTC. In addition, low expression of miR?486?5p in patients with PTC was associated with a worse overall survival. A total of 80 miR?486?5p?related genes were observed from at least 9 of 12 prediction platforms, and these were involved in 'hsa05200: Pathways in cancer' and 'hsa05206: MicroRNAs in cancer'. Finally, three hub genes, CRK like proto?oncogene, phosphatase and tensin homolog and tropomyosin 3, were identified as important candidates in tumorigenesis and progression of PTC. In conclusion, it may be hypothesized that miR?486?5p contributes towards PTC onset and progression, and may act as a clinical target. However, in vitro and in vivo experiments are required to validate the findings of the present study.

Dataset Information

Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.

Publications

Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells.

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