SM2miR: a database of the experimentally validated small molecules’ effects on microRNA expression

Liu, Xinyi; Wang, Shuyuan; Meng, Fengyan; Wang, Jizhe; Zhang, Yan; Dai, Erfu; Yu, Xuexin; Li, Xia; Jiang, Wei

doi:10.1093/bioinformatics/bts698

Cited by 186 publications

(153 citation statements)

References 17 publications

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“…For example, three other drugs, irbesartan, pseudoephedrine and vinblastine, can target JUN (Figure 6), indicating that the three drugs may affect the pan-cancer FFL JUN_hsa-miR-21-5p_MSH2 through mediating their drug target JUN as the mechanism of ATO. In addition, we obtained the drugs that can affect miRNA expression from the SM2miR database, which collects the experimentally validated small molecule drug effects on miRNA expression [72]. We found that the expression of hsa-miR-195-5p, hsa-miR-34a-5p and hsa-miR-21-5p could be regulated by some other FDA-approved drugs, suggesting that they might have the anticancer activity through modulating the pan-cancer FFLs.…”

Section: Resultsmentioning

confidence: 99%

Systematic dissection of dysregulated transcription factor–miRNA feed-forward loops across tumor types

Jiang¹,

Mitra²,

Chen³

et al. 2015

Briefings in Bioinformatics

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Transcription factor and microRNA (miRNA) can mutually regulate each other and jointly regulate their shared target genes to form feed-forward loops (FFLs). While there are many studies of dysregulated FFLs in a specific cancer, a systematic investigation of dysregulated FFLs across multiple tumor types (pan-cancer FFLs) has not been performed yet. In this study, using The Cancer Genome Atlas data, we identified 26 pan-cancer FFLs, which were dysregulated in at least five tumor types. These pan-cancer FFLs could communicate with each other and form functionally consistent subnetworks, such as epithelial to mesenchymal transition-related subnetwork. Many proteins and miRNAs in each subnetwork belong to the same protein and miRNA family, respectively. Importantly, cancer-associated genes and drug targets were enriched in these pan-cancer FFLs, in which the genes and miRNAs also tended to be hubs and bottlenecks. Finally, we identified potential anticancer indications for existing drugs with novel mechanism of action. Collectively, this study highlights the potential of pan-cancer FFLs as a novel paradigm in elucidating pathogenesis of cancer and developing anticancer drugs.

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Section: Resultsmentioning

confidence: 99%

Systematic dissection of dysregulated transcription factor–miRNA feed-forward loops across tumor types

Jiang¹,

Mitra²,

Chen³

et al. 2015

Briefings in Bioinformatics

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“…Although chemical approaches are a very young field in stem cell research, these small molecules exhibit a similar biological outcome to that achieved with the use of miRNAs in stem cell fate regulation [35] . Recently, small molecules have been correlated with endogenous miRNA expression and function [197][198][199][200][201][202] . Therefore, identifying the relationship between miRNAs and small molecules could provide new insights for drug development for regenerative medicine and elucidate detailed mechanisms of miRNA expression and function in the control of stem cell fate.…”

Section: Small Molecules and Stem Cell Fatementioning

confidence: 99%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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“…Along with the growth of miRNA transfection experiments, it is possible to regard the effects of the miRNA on gene expression at whole genome level, which more directly reflects alteration of gene expression affected by the perturbed miRNA. What's more, miREnvironment and SM2miR database have been constructed to collect the experimentally supported associations between small molecules and miRNAs [17, 18], Currently, miREnvironment database have collected complex interactions (3857 entries) among 1242 miRNAs, 305 phenotypes and 394 environment factors (including a few small molecules). SM2miR database have collected the 5160 records between 255 small molecules and 1680 miRNAs, and provided the effects (up-regulated and down-regulated) of small molecules on miRNA expression, and integrated all associations between drugs and miRNAs in miREnvironment database.…”

Section: Introductionmentioning

confidence: 99%

Identification of associations between small molecule drugs and miRNAs based on functional similarity

et al. 2016

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MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression at post-transcriptional level. Increasing evidences show aberrant expression of miRNAs in varieties of diseases. Targeting the dysregulated miRNAs with small molecule drugs has become a novel therapy for many human diseases, especially cancer. Here, we proposed a novel computational approach to identify associations between small molecules and miRNAs based on functional similarity of differentially expressed genes. At the significance level of p < 0.01, we constructed the small molecule and miRNA functional similarity network involving 111 small molecules and 20 miRNAs. Moreover, we also predicted associations between drugs and diseases through integrating our identified small molecule-miRNA associations with experimentally validated disease related miRNAs. As a result, we identified 2265 associations between FDA approved drugs and diseases, in which ~35% associations have been validated by comprehensive literature reviews. For breast cancer, we identified 19 potential drugs, in which 12 drugs were supported by previous studies. In addition, we performed survival analysis for the patients from TCGA and GEO database, which indicated that the associated miRNAs of 4 drugs might be good prognosis markers in breast cancer. Collectively, this study proposed a novel approach to predict small molecule and miRNA associations based on functional similarity, which may pave a new way for miRNA-targeted therapy and drug repositioning.

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SM2miR: a database of the experimentally validated small molecules’ effects on microRNA expression

Abstract: SM2miR is freely available at http://bioinfo.hrbmu.edu.cn/SM2miR/.

Cited by 186 publications

References 17 publications

Systematic dissection of dysregulated transcription factor–miRNA feed-forward loops across tumor types

Systematic dissection of dysregulated transcription factor–miRNA feed-forward loops across tumor types

MicroRNAs as novel regulators of stem cell fate

Identification of associations between small molecule drugs and miRNAs based on functional similarity

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