Dataset Information

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5-FAK axis.

ABSTRACT: microRNA-331-3p (miR-331-3p) has been displayed as an oncogene in pancreatic cancer (PC). The current research set out to elucidate how miR-331-3p in carcinoma-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) facilitated the tumorigenesis in PC. First, a dual-luciferase reporter assay was adopted to investigate the relationship between miR-331-3p and SCARA5. In addition, EVs were isolated normal fibroblasts and CAFs, and these isolated EVs were co-cultured with PC cells. Cell proliferative and migrating/invasive potentials were further evaluated with the help of a CCK-8 and Transwell assays, respectively. Gain- and loss-of-function assays were also implemented to assess the role of miR-331-3p, SCARA5, and FAK pathway in PC cells. Lastly, xenograft nude mice were established to investigate the role of miR-331-3p in vivo. miR-331-3p negatively targeted SCARA5 and was highly expressed in CAFs-derived EVs, which accelerated the proliferative, migrating, and invasive potentials of PC cells. Meanwhile, over-expression of miR-331-3p enhanced the proliferative, migrating, and invasive properties of PC cells and promoted tumor growth in vivo by manipulating SCARA5/FAK axis, whereas SCARA5 countered the oncogenic effects of miR-331-3p. Overall, miR-331-3p in CAFs-derived EVs inhibits SCARA5 expression and activates the FAK pathway, thereby augmenting the progression of PC. Our study provides a potential therapeutic target for the treatment of PC.

SUBMITTER: Han Y

PROVIDER: S-EPMC9090287 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer <i>via</i> the SCARA5-FAK axis.

Han Yadong Y Qian Xu X Xu Teng T Shi Yang Y

Cancer biology & therapy 20221201 1

microRNA-331-3p (miR-331-3p) has been displayed as an oncogene in pancreatic cancer (PC). The current research set out to elucidate how miR-331-3p in carcinoma-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) facilitated the tumorigenesis in PC. First, a dual-luciferase reporter assay was adopted to investigate the relationship between miR-331-3p and SCARA5. In addition, EVs were isolated normal fibroblasts and CAFs, and these isolated EVs were co-cultured with PC cells. Cell p ...[more]

PMID: 35510828

Similar Datasets

Project description:ObjectiveThis study explores LncRNA TM1-3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism.MethodsBioinformatics was performed to analyze OA disease-related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1-3P and miR-144-3p, ONECUT2 and miR-144-3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin-eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT-qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one-way analysis of variance of repeated measurement data was applied for multi-group comparison, following Tukey's post-test.ResultsONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1-3P were increased, and expression of miR-144-3p was decreased in interleukin (IL)-1β-induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR-144-3p down-regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL-1β (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1-3P up-regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR-144-3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1-3P attenuated the injury of knee joint tissue, down-regulated the expression of ONECUT2, Smurf2, IL-1β, IL-6, TNF-α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05).ConclusionLncRNA TM1-3P improved inflammation and damage of knee joints in OA rats through miR-144-3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA.

Project description:PURPOSE:Triple-negative breast cancer is characterized by fast progression with high possible for metastasis and poor survival. Dysfunction of microRNAs plays an important role in the initiation and progression of cancer. Our previous microRNA-seq data indicated the downregulation of miR-331-3p in triple-negative breast cancer tissues compared with that of the noncancer tissues. However, the function of miR-331-3p in triple-negative breast cancer remains largely unknown. Herein, the involvement of miR-331-3p in triple-negative breast cancer was investigated and the therapeutic potential of miR-331-3p was also explored. METHODS:Real-time quantitative polymerase chain reaction was performed to detect the expression of miR-331-3p in triple-negative breast cancer tissues and cell lines. The cell proliferation was determined by the cell counting kit-8 assay. Apoptosis of triple-negative breast cancer cells was examined by annexin V/propidium iodide staining. miRDB database was used to predict the potential targets of miR-331-3p. Western blot was performed to examine the expression of the target protein. RESULTS:miR-331-3p was significantly downregulated in triple-negative breast cancer tissues and cell line. Lower miR-331-3p expression was significantly correlated with the tumor size, TNM stage, and lymph node metastasis of patients with triple-negative breast cancer. Functional experiments showed that the overexpression of miR-331-3p inhibited the proliferation and increased apoptosis of triple-negative breast cancer cells. Neuropilin-2 was identified as a target of miR-331-3p, which harbored binding site of miR-331-3p in its 3'-untranslated region. Overexpression of miR-331-3p decreased the messenger RNA and protein levels of neuropilin-2 in triple-negative breast cancer cells. Restoration of neuropilin-2 partially reversed the inhibitory effects of miR-331-3p on the proliferation of triple-negative breast cancer cells. CONCLUSIONS:Our results demonstrated the novel function of miR-331-3p/neuropilin-2 signaling in regulating the malignant behaviors of triple-negative breast cancer cells, which suggested miR-331-3p as a potential target for the treatment of triple-negative breast cancer.

Dataset Information

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5-FAK axis.

Publications

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer <i>via</i> the SCARA5-FAK axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets