Dataset Information

Stemness-Attenuating miR-503-3p as a Paracrine Factor to Regulate Growth of Cancer Stem Cells.

ABSTRACT: Cancer stem cells (CSCs) with self-renewal abilities endorse cellular heterogeneity, resulting in metastasis and recurrence. However, there are no promising therapeutics directed against CSCs. Herein, we found that miR-503-3p inhibited tumor growth via the regulation of CSC proliferation and self-renewal. miR-503-3p, isolated from human adipose stem cell- (ASC-) derived exosomes, suppressed initiation and progression of CSCs as determined by anchorage-dependent (colony formation) and anchorage-independent (tumorsphere formation) assays. The expression of pluripotency genes was significantly decreased in miR-503-3p-treated CSCs. Furthermore, xenografts, which received miR-503-3p, exhibited remarkably reduced tumor growth in vivo. Thus, miR-503-3p may function as a stemness-attenuating factor via cell-to-cell communications.

SUBMITTER: Seo M

PROVIDER: S-EPMC5904772 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Stemness-Attenuating miR-503-3p as a Paracrine Factor to Regulate Growth of Cancer Stem Cells.

Seo Minkoo M Kim Seung Min SM Woo Eun Young EY Han Ki-Cheol KC Park Eun Joo EJ Ko Seongyeol S Choi Eun Wook EW Jang Mihue M

Stem cells international 20180404

Cancer stem cells (CSCs) with self-renewal abilities endorse cellular heterogeneity, resulting in metastasis and recurrence. However, there are no promising therapeutics directed against CSCs. Herein, we found that miR-503-3p inhibited tumor growth via the regulation of CSC proliferation and self-renewal. miR-503-3p, isolated from human adipose stem cell- (ASC-) derived exosomes, suppressed initiation and progression of CSCs as determined by anchorage-dependent (colony formation) and anchorage-i ...[more]

PMID: 29849663

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Project description:Growth plate chondrocytes undergo sequential differentiation to form the resting zone, the proliferative zone (PZ), and the hypertrophic zone (HZ). The important role of microRNAs (miRNAs) in the growth plate was previously revealed by cartilage-specific ablation of Dicer, an enzyme essential for biogenesis of many miRNAs. To identify specific miRNAs that regulate differentiation of PZ chondrocytes to HZ chondrocytes, we microdissected individual growth plate zones from juvenile rats and performed miRNA profiling using a solution hybridization method and miRNA sequencing. Thirty-four miRNAs were differentially expressed between the PZ and the HZ, and we hypothesized that some of the miRNAs that are preferentially expressed in the PZ may promote proliferation and inhibit hypertrophic differentiation. Consistent with this hypothesis, transfection of inhibitors for four of these miRNAs (mir-369-3p, mir-374-5p, mir-379-5p, and mir-503-5p) decreased proliferation in primary epiphyseal chondrocytes. The inhibitors for three of these miRNAs (mir-374-5p, mir-379-5p, and mir-503-5p) also increased expression of multiple genes that are associated with chondrocyte hypertrophic differentiation. We next hypothesized that preferential expression of these miRNAs in the PZ is driven by the parathyroid hormone-related protein (PTHrP) concentration gradient across the growth plate. Consistent with this hypothesis, treatment of primary chondrocytes with a parathyroid hormone (PTH)/PTHrP receptor agonist, PTH1-34, increased expression of mir-374-5p, mir-379-5p, and mir-503-5p. Taken together, our findings suggest that the PTHrP concentration gradient across the growth plate induces differential expression of mir-374-5p, mir-379-5p, and mir-503-5p between the PZ and the HZ. In the PZ, the higher expression levels of these miRNAs promote proliferation and inhibit hypertrophic differentiation. In the HZ, downregulation of these miRNAs inhibits proliferation and promotes hypertrophic differentiation.

Dataset Information

Stemness-Attenuating miR-503-3p as a Paracrine Factor to Regulate Growth of Cancer Stem Cells.

Publications

Stemness-Attenuating miR-503-3p as a Paracrine Factor to Regulate Growth of Cancer Stem Cells.

Similar Datasets

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