Towards the human cellular microRNAome

McCall, Matthew N.; Kim, Min‐Sik; Adil, Mohammed; Patil, Arun H.; Lu, Yin; Mitchell, Christopher J.; Leal-Rojas, Pamela; Xu, Jinling; Kumar, Manoj; Dawson, Valina L.; Dawson, Ted M.; Baras, Alexander S.; Rosenberg, Avi Z.; Arking, Dan E.; Burns, Kathleen H.; Pandey, Akhilesh Kumar; Halushka, Marc K.

doi:10.1101/120394

Cited by 10 publications

(14 citation statements)

References 46 publications

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“…We found that miR-486 was expressed in OE neurons by histologic analysis, and miR-486 inhibited neuron production in a primary culture over-expression assay. While miR-486 has been reported as highly expressed in blood cells [ 40 , 41 ], our results on miR-486 expression in neuronal cells are supported by two other reports that found miR-486 expressed in motor neurons [ 42 ] and iPSC-generated dopaminergic neurons [ 41 , 43 ]. Our functional results are in line with a study showing that up-regulation of miR-486 following spinal cord injury promoted neurodegeneration [ 42 ].…”

Section: Discussionsupporting

confidence: 89%

Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium

et al. 2017

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Despite a robust capacity for adult neurogenesis in the olfactory epithelium (OE), olfactory sensory losses are common. Identification of mechanisms regulating adult OE neurogenesis is, therefore, of interest. MicroRNAs (miRNAs) are broadly important in regulating vertebrate neurodevelopment, and are required in embryonic olfactory differentiation. We report here that a panel of miRNAs is differentially expressed by either progenitor or progeny cells in the regenerating mouse OE. Progenitor cells were purified from lesioned OE based on c-Kit expression, and miRNA expression was assayed in c-Kit (+) and c-Kit (-) cell populations. 28 miRNAs were significantly downregulated by at least 4 fold in the c-Kit (+) fraction, which marks the globose basal progenitor cell population. In addition, 10 miRNAs were upregulated in these basal cells. MiR-486, the most strongly downregulated miRNA identified, was further characterized to verify results. MiR-486 expression was confirmed in the c-Kit (-) OE layers using in situ hybridization. As a functional assay, over-expression of miR-486 in purified c-Kit (+) basal cell cultures resulted in a reduction in neurogenesis, consistent with a possible negative feedback regulatory model. Our data provide new insights regarding miRNA expression and function during adult OE neurogenesis, and identify candidate miRNAs warranting further study.

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Section: Discussionsupporting

confidence: 89%

Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium

et al. 2017

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“…Scale bars of 940 and 9400 represent 1 mm and 100 µm, respectively. McCall et al, 2017). However, our recent studies have shown that some passenger miRNA have tumor-suppressive functions in cancer cells (e.g.…”

Section: Discussionmentioning

confidence: 99%

RNA‐sequence‐based microRNA expression signature in breast cancer: tumor‐suppressive miR‐101‐5p regulates molecular pathogenesis

et al. 2019

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Aberrantly expressed microRNA (miRNA) are known to disrupt intracellular RNA networks in cancer cells. Exploring miRNA-dependent molecular networks is a major challenge in cancer research. In this study, we performed RNA-sequencing of breast cancer (BrCa) clinical specimens to identify tumor-suppressive miRNA in BrCa. In total, 64 miRNA were identified as candidate tumor-suppressive miRNA in BrCa cells. Analysis of our BrCa signature revealed that several miRNA duplexes (guide strand/passenger strand) derived from pre-miRNA were downregulated in BrCa tissues (e.g. miR-99a-5p/-3p, miR-101-5p/-3p, miR-126-5p/-3p, miR-143-5p/-3p, and miR-144-5p/-3p). Among these miRNA, we focused on miR-101-5p, the passenger strand of pre-miR-101, and investigated its tumor-suppressive roles and oncogenic targets in BrCa cells. Low expression of miR-101-5p predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0316). Ectopic expression of miR-101-5p attenuated aggressive phenotypes, e.g. proliferation, migration, and invasion, in BrCa cells. Finally, we identified seven putative oncogenic genes (i.e. High Mobility Group Box 3, Epithelial splicing regulatory protein 1, GINS complex subunit 1 (GINS1), Tumor Protein D52, Serine/Arginine-Rich Splicing Factor Kinase 1, Vang-like protein 1, and Mago Homolog B) regulated by miR-101-5p in BrCa cells. The expression of these target genes was associated with the molecular pathogenesis of BrCa. Furthermore, we explored the oncogenic roles of GINS1, whose function had not been previously elucidated, in BrCa cells. Aberrant expression of GINS1 mRNA and protein was observed in BrCa clinical specimens, and high GINS1 expression significantly predicted poor prognosis in patients with BrCa (overall survival rate: P = 0.0126). Knockdown of GINS1 inhibited the malignant features of BrCa cells. Thus, identification of tumor-suppressive miRNA and molecular networks controlled by these miRNA in Abbreviations BrCa, breast cancer; ESRP1, Epithelial splicing regulatory protein 1; GEO, Gene Expression Omnibus; GINS1, GINS complex subunit 1; HMGB3, High Mobility Group Box 3; MAGOHB, Mago Homolog B; miRNA, microRNA; RISC, RNA-induced silencing complex; SRPK1, Serine/Arginine-Rich Splicing Factor Kinase 1; TCGA, The Cancer Genome Atlas; TPD52, Tumor Protein D52; VANGL1, Vang-like protein 1.426 Molecular Oncology 14 (2020) 426-446 ª

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“…In addition, CXCL12 has been shown to be angiogenic in various tumors (Koshiba et al, 2000;Kryczek et al, 2005). Of note, miR-141-3p has been found to be expressed in mammary epithelial cells themselves (McCall et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer

et al. 2019

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One of the hallmarks of cancer is sustained angiogenesis. Favorable results have been reported in some breast cancer (BC) patients receiving antiangiogenic therapy with bevacizumab (Bev) in combination with chemotherapy, and further knowledge on how Bev can be optimally combined with conventional treatment to increase efficacy is strongly needed. In this randomized, neoadjuvant phase II clinical trial, 132 patients with HER2‐negative, nonmetastatic BC were treated with Bev in combination with sequential chemotherapy. Biopsies were sampled before treatment, after 12 weeks with anthracycline and after taxane therapy at week 25. MicroRNA (miRNA) expression profiling was performed on biopsies from each time point. Altogether, 241 biopsies were analyzed with the aim of identifying miRNA‐based biomarkers of response to therapy. Results from the miRNA analyses were reported for the ER‐positive cohort, which were previously demonstrated to benefit from antiangiogenic therapy in this study. For both treatment arms of this cohort, significantly different expression was observed for 217 miRNAs between objective responding and nonresponding patients before treatment initiation. These miRNAs have been linked to regulation of epithelial–mesenchymal transition, metastasis, and tumor growth, among other processes. Bev in combination with chemotherapy resulted in similar miRNA changes to chemotherapy alone. However, the deregulation of miRNA expression occurred earlier in the Bev arm. In both arms, tumor suppressor miRNAs were found upregulated after treatment, while oncogenic miRNAs were downregulated in the Bev arm. Patients responding to Bev showed a strong correlation between deregulated miRNAs and decreased proliferation score during the course of treatment, with downregulation of miR‐4465 as the strongest indicator of reduced proliferation. Integrative analyses at miRNA‐, gene‐, and protein expression further indicated a longitudinal decrease in proliferation. Altogether, the results indicate that proliferation might represent a predictive factor for increased Bev sensitivity, which may aid in the identification of patients who could potentially benefit from Bev.

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Towards the human cellular microRNAome

Cited by 10 publications

References 46 publications

Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium

Differential expression of microRNAs among cell populations in the regenerating adult mouse olfactory epithelium

RNA‐sequence‐based microRNA expression signature in breast cancer: tumor‐suppressive miR‐101‐5p regulates molecular pathogenesis

miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer

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