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Comparative profiling of mRNA expression in human mesenchymal stem cells derived from adult adipose and lipoma tissues

ABSTRACT: Human mesenchymal stem cells (MSCs) have been isolated from adult adipose tissues, and were shown to have ability to differentiate into multiple mesodermal lineages as well as non-mesodermal lineages. MSC had also been isolated from lipoma, and the lipoma-derived MSCs (LM6) showed very similar stem cell characteristics to adipose-derived MSCs (AM3). However, LM6 cells exhibited a higher cumulative population doubling levels as compared with AM3 cells. The expression profiles of both mRNAs and microRNAs (miRNAs) from AM3 and LM6 cells were compared to find considerable similarities except that miRNAs miR-99a and miR-152 were abundantly expressed in AM3, but absent in LM6 cells. The abundantly differentially expressed genes HAS2, VNN1, SLC16A6 and COL11A1 in LM6 cells were shown to be targets of miRNAs miR-99a and/or miR-152. Several additional genes were also found to be targets of miRNAs miR-99a and miR-152, as well as let-7g, let-7i, miR-199a, mir-134 and miR-374. The highly up-regulated expression of miRNA target genes such as SLC16A6, COL11A1 and TRHDE, as well as several other genes such as sushi domain containing 2, keratin associated proteins and tumor necrosis factor family, may explain the higher proliferation potential in LM6 cells compared with AM3 cells. Keywords: genetic modification The expression profiles of both mRNAs and miRNAs from the same RNA samples of AM3 and LM6 cells were determined and compared in order to understand the genetic bases for their similarities and differences.

ORGANISM(S): Homo sapiens

SUBMITTER: Sung-Liang Yu

PROVIDER: E-GEOD-12843 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Comparative profiling of mRNA expression in human mesenchymal stem cells derived from adult adipose and lipoma tissues

Project description:Human mesenchymal stem cells (MSCs) have been isolated from adult adipose tissues, and were shown to have ability to differentiate into multiple mesodermal lineages as well as non-mesodermal lineages. MSC had also been isolated from lipoma, and the lipoma-derived MSCs (LM6) showed very similar stem cell characteristics to adipose-derived MSCs (AM3). However, LM6 cells exhibited a higher cumulative population doubling levels as compared with AM3 cells. The expression profiles of both mRNAs and microRNAs (miRNAs) from AM3 and LM6 cells were compared to find considerable similarities except that miRNAs miR-99a and miR-152 were abundantly expressed in AM3, but absent in LM6 cells. The abundantly differentially expressed genes HAS2, VNN1, SLC16A6 and COL11A1 in LM6 cells were shown to be targets of miRNAs miR-99a and/or miR-152. Several additional genes were also found to be targets of miRNAs miR-99a and miR-152, as well as let-7g, let-7i, miR-199a, mir-134 and miR-374. The highly up-regulated expression of miRNA target genes such as SLC16A6, COL11A1 and TRHDE, as well as several other genes such as sushi domain containing 2, keratin associated proteins and tumor necrosis factor family, may explain the higher proliferation potential in LM6 cells compared with AM3 cells. Keywords: genetic modification

2009-09-08 | GSE12843 | GEO

miR-99a let7c cluster

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2013-07-01 | E-MEXP-3748 | biostudies-arrayexpress

Expression data from ETV6-RUNX1-positive Reh leukemic cells after overexpression of miR-125b, miR-100 and miR-99a levels in different combinations

Project description:Combined overexpression of miR-125b with miR-99a and/or miR-100 induced VCR resistance in ETV6-RUNX1-positive leukemic cells Reh. We used microarrays to detail the global changes in gene expression of Reh cells upon enforced expression of miR-125 per se compared with combination of overexpression of miR-125b, miR-100 and/or miR-99a MiR-99a and/or miR-100 were transiently overexpressed in stable miR-125b-expressing and stable scrambled miR-control-expressing Reh cells. Cellular resistance to VCR was determined by MTT assay after incubating the cells with 9 ng/mL VCR for 3 days. Changes in the gene expression pattern of Reh cells induced by miRNAs overexpression were measured using Affymetrix Arrays.

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Project description:Although regulation of stem cell homeostasis by miRNAs is well studied, it is unclear how individual miRNAs, genomically encoded within an organized polycistron, can interact to induce an integrated phenotype. miR-99a/100, let-7 and miR-125b paralogues are encoded in two tricistrons on human chromosome 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Integrative analysis of global gene expression profiling, miRNA target prediction and pathway architecture revealed that miR-99a/100, let-7 and miR-125b functionally converge at the combinatorial block of the TGFM-NM-2 pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, downregulation of tumor suppressor genes APC/APC2 stabilizes active M-NM-2-Catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFM-NM-2 signaling the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo, while favoring megakaryocytic differentiation. We lentivirally transduced cord blood CD34+-hematopoietic stem and progenitor cells (CB-HSPCs) to ectopically express miR-125b-2, miR-99a, let-7c or miR-99a~125b-2 and cultured them in megakaryocytic differentiation medium for 7 days.

2014-03-28 | E-GEOD-56335 | biostudies-arrayexpress

Prostate cancer-derived small extracellular vesicles promote osteoclastogenesis and cancer-induced osteolysis via miR-152-3p delivery

Project description:Extracellular vesicles (EVs) play critical roles in regulating bone metastatic microenvironment through mediating intercellular communications. Here, we report a direct regulatory mode between tumor cells and osteoclasts in osteolytic metastasis of prostate cancer via vesicular miRNAs transfer. Combined analysis of miRNAs profiles both in tumor-derived small EVs (sEVs) and osteoclasts identified miR-152-3p as a potential osteolytic molecules. Further in vitro experiments showed that sEVs were enriched in miR-152-3p, which targets osteoclastogenic regulator MAFB. Blocking miR-152-3p in sEVs upregulated the expression of MAFB and impaired osteoclastogenesis in recipient osteoclasts. In vivo xenograft mouse model found that blocking of miR-152-3p in sEVs significantly rescued the loss of trabecular architecture, while systemic inhibition of miR-152-3p using antagomiR-152-3p reduced the osteolytic lesions of cortical bone while remaining the basic trabecular architecture. Together, our findings suggest that miR-152-3p carried by prostate cancer-derived sEVs deliver osteolytic signals from tumor cells to osteoclasts, facilitating osteolytic progression in bone metastasis.

2021-02-24 | GSE161419 | GEO

Differentiating liposarcoma from lipoma using a simple blood test: A miRNA signature

Project description:Background: Liposarcoma constitute about 13% of all soft tissue sarcoma and are associated with a high risk of metastases. As the preoperative differentiation between benign and malign lipomatous tumors is restricted to magnetic resonance imaging, computed tomography and biopsy, we performed a miRNA array to distinguish liposarcoma patients from healthy controls and lipoma patients. Workflow: Blood samples of patients with dedifferentiated liposarcoma, healthy controls and lipoma patients were collected. Whole blood RNA was extracted and samples of patients with dedifferentiated liposarcoma (n=6) and of healthy donors (n=4) were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm the most differentially expressed miRNA; being further analyzed in an independent cohort of healthy controls as well as in lipoma patients. Results: As shown by the microarray, two miRNAs (miR-4668-5p and miR-3613-3p) were shown to be significantly upregulated (fold change: >2.5; p<0.05) in patients with dedifferentiated liposarcoma (n=6) as compared to healthy controls (n=4). miR-4668-5p was further validated by qRT-PCR to be significantly upregulated in liposarcoma patients compared to an independent cohort of healthy controls (n=3) and lipoma patients (n=6). Conclusion: We identified a specific whole blood miRNA (miR-4668-5p) that may serve to distinguish between lipoma and liosarcoma patients, thus potentially serving as a specific biomarker for dedifferentiated liposarcoma.

2018-06-01 | E-MTAB-5126 | biostudies-arrayexpress

Expression data after miR-99a transfection in C4-2 prostate cancer cells

Project description:MicroRNAs (miRNAs) have been globally profiled in cancers but there tends to be poor agreement between studies including in the same cancers. Additionally, few putative miRNA targets have been validated. To overcome the lack of reproducibility, we profiled miRNAs by next generation sequencing and locked nucleic acid miRNA microarrays, and we verified concordant changes by quantitative RT-PCR. Notably, miR-125b and the miR-99 family members miR-99a, -99b, -100 were down-regulated in all assays in advanced prostate cancer cell lines relative to the parental cell lines from which they were derived. All four miRNAs were also down-regulated in human prostate tumor tissue compared to normal prostate. Transfection of miR-99a, -99b or -100 inhibited the growth of prostate cancer cells and decreased the expression of prostate-specific antigen (PSA), suggesting potential roles as tumor suppressors in this setting. To identify targets of these miRNAs, we combined computational prediction of potential targets with experimental validation by microarray and polyribosomal loading analysis. Three direct targets of the miR-99 family that were validated in this manner were the chromatin remodeling factors SMARCA5 and SMARCD1 and the growth regulatory kinase mTOR. We determined that PSA is post-transcriptionally regulated by the miR-99 family members at least partially by repression of SMARCA5. Together, our findings suggest key functions and targets of miR-99 family members in prostate cancer suppression and prognosis. C4-2 cells were transfected with miR-99a and harvested after 48hr. si-GL2 was used as control.

2010-12-29 | E-GEOD-26332 | biostudies-arrayexpress

MicroRNA-204-5p is a tumor suppressor and potential therapeutic target in head and neck squamous cell carcinoma

Project description:To screen microRNAs (miRNAs) that are deregulated in head and neck squamous cell carcinoma (HNSCC), we comparatively analyzed the miRNA profiles by using 10 HNSCC patient samples and paired adjacent non-cancerous counterparts. Microarray analysis revealed that 24 miRNAs were downregulated and 19 miRNAs were elevated in HNSCC samples when compared with adjacent non-cancerous tissue. These miRNAs included upregulated miR-21-5p, miR-21-3p, and downregulated miR-99a-5p, which have been reported to regulate malignant progression of HNSCC in previous studies.

2020-01-21 | GSE124566 | GEO

miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFβ and Wnt signaling

Project description:Although regulation of stem cell homeostasis by miRNAs is well studied, it is unclear how individual miRNAs, genomically encoded within an organized polycistron, can interact to induce an integrated phenotype. miR-99a/100, let-7 and miR-125b paralogues are encoded in two tricistrons on human chromosome 11 and 21. They are highly expressed in hematopoietic stem cells (HSCs) and acute megakaryoblastic leukemia (AMKL), an aggressive form of leukemia with poor prognosis. Integrative analysis of global gene expression profiling, miRNA target prediction and pathway architecture revealed that miR-99a/100, let-7 and miR-125b functionally converge at the combinatorial block of the TGFβ pathway by targeting four receptor subunits and two SMAD signaling transducers. In addition, downregulation of tumor suppressor genes APC/APC2 stabilizes active β-Catenin and enhances Wnt signaling. By switching the balance between Wnt and TGFβ signaling the concerted action of these tricistronic miRNAs promoted sustained expansion of murine and human HSCs in vitro or in vivo, while favoring megakaryocytic differentiation.

2014-03-28 | GSE56335 | GEO

Differentially expressed genes after miRNA or siRNA transfection in human cancer cell lines Panc-1, FaDu and PC3

Project description:To identify differentially expressed genes by anti cancer treatments (microRNAs or siRNAs) in human cancer, several cell lines (pancreatic cancer, hypopharyngeal squamous cell carcinoma and prostate cancer) were subjected to Agilent whole genome microarrays. Human cell lines (Panc-1, FaDu and PC3) were treated with miRNAs (miR99a-5p, miR-99a-3p, miR-100-3p, miR-150-5p and miR-150-3p), siRNAs (si-FOXQ1).

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