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Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis.

ABSTRACT: Exosomes are an important carrier for cell communication. miRNAs in exosomes are potential biomarkers and therapeutic targets in different types of cancer. However, the role of exosomal miRNAs in medulloblastoma (MB) patients is largely unknown. In this study, we reported that there was a higher level of miR-130b-3p in exosomes derived from MB patient plasma compared with exosomes from healthy control plasma. Exosomes from MB patient plasma could transfer miR-130b-3p to an MB cell line and played suppressor roles for cell proliferation. miR-130b-3p suppressed MB tumorigenesis by targeting a previously unknown target, serine/threonine-protein kinase 1 (SIK1), through the p53 signaling pathways. In addition, we found an unreported role of SIK1 in promoting MB tumor growth and an SIK1 inhibitor could inhibit MB cell proliferation. This research provides new insight into the molecular mechanism of MB and may provide a new therapeutic strategy for MB treatment.

SUBMITTER: Huang S

PROVIDER: S-EPMC7264172 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis.

Huang Saihua S Xue Ping P Han Xiao X Zhang Caiyan C Yang Lan L Liu Lijuan L Wang Xiang X Li Hao H Fu Jinrong J Zhou Yufeng Y

Cell death & disease 20200601 6

Exosomes are an important carrier for cell communication. miRNAs in exosomes are potential biomarkers and therapeutic targets in different types of cancer. However, the role of exosomal miRNAs in medulloblastoma (MB) patients is largely unknown. In this study, we reported that there was a higher level of miR-130b-3p in exosomes derived from MB patient plasma compared with exosomes from healthy control plasma. Exosomes from MB patient plasma could transfer miR-130b-3p to an MB cell line and playe ...[more]

PMID: 32483145

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Project description:BackgroundColorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear.MethodsCRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils.ResultsOur study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition. Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor-β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF-β1 axis.ConclusionOur study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

Dataset Information

Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis.

Publications

Exosomal miR-130b-3p targets SIK1 to inhibit medulloblastoma tumorigenesis.

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