Constitutive expression of microRNA-150 in mammary epithelium suppresses secretory activation and impairs <i>de novo</i> lipogenesis

Heinz, Richard E.; Rudolph, Michael C.; Ramanathan, Palaniappan; Spoelstra, Nicole S.; Butterfield, Kiel; Webb, Patricia G.; Babbs, Beatrice; Gao, Hongwei; Chen, Shang; Gordon, Michael A.; Anderson, Steve M.; Neville, Margaret C.; Gu, Haihua; Richer, Jennifer K.

doi:10.1242/dev.139642

Cited by 21 publications

(23 citation statements)

References 65 publications

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“…miR-150 was previously reported to play important roles in controlling B cell differentiation by targeting the transcription factor c-Myb (28). Moreover, miR-150 has been reported to regulate de novo lipogenesis by targeting Fasn and other lipid-related genes in mammary epithelium (29). Here, we uncover a potentially novel role for miR-150 in macrophages to regulate cholesterol metabolism and lipid trafficking genes involved in AMD based on our RNA-Seq results.…”

Section: Discussionmentioning

confidence: 57%

Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

Lin¹,

Moolani²,

Sène³

et al. 2018

JCI Insight

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Macrophage aging is pathogenic in diseases of the elderly, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. However, the role of microRNAs, which modulate immune processes, in regulating macrophage dysfunction and thereby promoting age-associated diseases is underexplored. Here, we report that microRNA-150 (miR-150) coordinates transcriptomic changes in aged murine macrophages, especially those associated with aberrant lipid trafficking and metabolism in AMD pathogenesis. Molecular profiling confirmed that aged murine macrophages exhibit dysregulated ceramide and phospholipid profiles compared with young macrophages. Of translational relevance, upregulation of miR-150 in human peripheral blood mononuclear cells was also significantly associated with increased odds of AMD, even after controlling for age. Mechanistically, miR-150 directly targets stearoyl-CoA desaturase-2, which coordinates macrophage-mediated inflammation and pathologic angiogenesis, as seen in AMD, in a VEGF-independent manner. Together, our results implicate miR-150 as pathogenic in AMD and provide potentially novel molecular insights into diseases of aging.

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Section: Discussionmentioning

confidence: 57%

Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

Lin¹,

Moolani²,

Sène³

et al. 2018

JCI Insight

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“…We also checked expression of miR-134, miR-150-5p and miR-200a, which reportedly regulate STAT5b expression [30][31][32] in X-ray irradiation HeLa cells. The expression of miR-34a, who is up-regulated after irradiation [14], was used as a reference of radiation treatment.…”

Section: Ionizing Radiation-induced Mir-5094 Expression Results In Stmentioning

confidence: 99%

“…It was reported that miR-200a directly repressed STAT5b expression in both mice and human [30], while miR-134 was showed to inhibit proliferation, survival and xenograft growth in cancer cell and stem-cell by targeting STAT5b and KRAS [31]. Similarly, miR-150 was demonstrated to suppress expression of STAT5b in mammary epithelial cells of bitransgenic mice [32]. Whether and how miRNAs regulate STAT5b in DNA damage response to IR remains to be an open question.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

The Role of MiR-5094 as a Proliferation Suppressor during Cellular Radiation Response via Downregulating STAT5b

Ding

Hua

et al. 2020

J. Cancer

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MicroRNAs (miRNAs) play important roles in the regulation of cellular stress responses. We previously uncovered 10 novel human miRNAs which are induced by X-ray irradiation in HeLa cells using Solexa deep sequencing. The most highly expressed new miRNA, miR-5094, was predicted to target STAT5b. This study wonders whether miR-5094 participates in cellular radiation response via STAT5b. Firstly, direct interaction between miRNA-5094 and the STAT5b 3'-UTR was confirmed by luciferase reporter assay. Then, the radiation responsive expression of miR-5094 and STAT5b were measured in HeLa and Jurkat cells, and the expressions of downstream genes of STAT5b after ionizing radiation (IR) were detected in HeLa cells. At last, the effects of miR-5094 on survival fraction, cell proliferation, cell cycle arrest and apoptosis induced by IR were investigated in HeLa cells, Jurkat cells and human peripheral blood T cells. It was found that up-regulation of miR-5094 by radiation induction or miRNA mimic transfection suppressed expression of STAT5b, and consequently decreased the transcription of downstream Igf-1 and Bcl-2. Additionally, over expression of miR-5094 resulted in proliferation suppression and knockdown of miR-5094 by miRNA inhibitor after irradiation partially reversed the proliferation suppression induced by miR-5094 in HeLa cells, Jurkat cells and CD4 + T cells. Collectively, our findings demonstrate that up-regulation of miR-5094 down-regulated the expression of STAT5b, thereby suppressing cell proliferation after X-ray irradiation.

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“…Additionally, the previous studies offered us reliable experimental buttress to the prediction in our ceRNA network. The FASN-3'-UTRluciferase assay was successfully performed to validate the ability of miR-150-5p to target FASN in the mice experiment 52 . MiR-21 was able to induce the tumor growth by targeting TGFBI in non-small cell lung cancer cells 53 and pancreatic cancer cells 54 , demonstrating the relative stability of our predictions though experimental investigation in BLCA is demanded.…”

Section: Discussionmentioning

confidence: 99%

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

Zhou¹,

Tian²,

Yang³

et al. 2020

Preprint

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Background: Immunotherapy has been proved to be effective for bladder cancer (BLCA). However, the molecular network involved in BLCA tumor immune response remains unclear. This study aims to construct an immune-related ceRNA network and to identify the prognostic value. Methods: Based on The Cancer Genome Atlas (TCGA), we used single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network analysis (WGCNA) to determine immune-related mRNA, lncRNA and miRNA. Then least absolute shrinkage, and selection operator (LASSO) and Cox regression were performed to identify the mRNAs with high prognostic value, and accordingly, the risk score was calculated. Internal and external validation were performed both in TCGA and GSE13507 with Kaplan-Meier (KM) survival and Receiver Operating Characteristic (ROC) curve analysis. Using the immune-related mRNA, lncRNA and miRNA, a ceRNA network was established via MiRcode, starBase, miRDB, miRTarBase and TargetScan. Besides, we also explore the relationship between the risk score and immune cell infiltration via CIBERSORT algorithm. Results: 5 mRNAs (PCGF3, FASN, DPYSL2, TGFBI and NTF3) were ultimately identified, and KM survival analysis displayed the 5-mRNA risk signature could predict the prognosis of BLCA with high efficacy both in TCGA (p = 1.006e-13) and GSE13507 (p = 7.759e-04). Using miRNA targeting molecular prediction database, an immune-related ceRNA network, including 5 mRNAs, 24 miRNAs and 86 lncRNAs, was constructed. Memory B cells, activated dendritic cells, and regulatory T cells infiltration into tumors were negatively correlated with risk score, while the infiltration levels of macrophages M0, M1 and M2 were positively correlated with risk score. Conclusion: This study helped to better understand the molecular mechanisms of tumor immune response from the view of ceRNA hypothesis, and provided a novel prognostic signature for bladder cancer.

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Constitutive expression of microRNA-150 in mammary epithelium suppresses secretory activation and impairs de novo lipogenesis

Cited by 21 publications

References 65 publications

Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

The Role of MiR-5094 as a Proliferation Suppressor during Cellular Radiation Response via Downregulating STAT5b

Construction of An Immune-Related CeRNA Network as a Prognostic Signature in Bladder Cancer

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