Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Xu, Chen; Chen, Yu; Zhang, Hao; Chen, Yuanyuan; Shen, Xiantao; Shi, Changgui; Liu, Yang; Yuan, Wen

doi:10.1038/srep21580

Cited by 44 publications

(54 citation statements)

References 35 publications

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“…KEGG pathway analyses were performed as previously described 23. An adjusted P-value that is lower than 0.05 indicated a statistically significant deviation from the expected distribution, and thus the corresponding KEGG pathways were enriched in target genes.…”

Section: Methodsmentioning

confidence: 99%

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

Luo¹,

Wang²,

Tang³

et al. 2017

J. Cancer

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Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy.

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Section: Methodsmentioning

confidence: 99%

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

Luo¹,

Wang²,

Tang³

et al. 2017

J. Cancer

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“…We calculated the P value of each GO term using right-sided hypergeometric tests, and Benjamini-Hochberg adjustment was used for multiple test correction5960. We consider those terms with a P value < 0.05 as significantly enriched terms.…”

Section: Methodsmentioning

confidence: 99%

Microcystin-Leucine Arginine Causes Cytotoxic Effects in Sertoli Cells Resulting in Reproductive Dysfunction in Male Mice

Chen

Zhou

Wang

et al. 2016

Sci Rep

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Microcystin-leucine arginine (MC-LR) is a potent toxin for Sertoli cells. However, the specific molecular mechanisms of MC-induced cytotoxicity still remain unclear. In this study, we performed a comprehensive analyses of changes of miRNAs and mRNAs in Sertoli cells treated with MC-LR. Through computational approaches, we showed the pivotal roles of differentially expressed miRNAs that were associated with cell metabolism, cellular growth and proliferation, cell-to-cell signaling and interaction and cellular movement. Ingenuity Pathway Analyses (IPA) revealed some differentially expressed miRNAs and mRNAs that may cause reproductive system diseases. Target gene analyses suggested that destruction in tight junctions (TJ) and adherens junctions (AJ) in testes may be mediated by miRNAs. Consistent with a significant enrichment of chemokine signaling pathways, we observed numerous macrophages in the testes of mice following treatment with MC-LR, which may cause testicular inflammation. Moreover, miR-98-5p and miR-758 were predicted to bind the 3′-UTR region of the mitogen-activated protein kinase 11 (MAPK11, p38 β isoform) gene which stimulates tumor necrosis factor-α (TNF-α) expression in Sertoli cells. TNF-α could interact with the tumor necrosis factor receptor 1 (TNFR1) on germ cells leading to induction of germ cell apoptosis. Collectively, our integrated miRNA/mRNA analyses provided a molecular paradigm, which was experimentally validated, for understanding MC-LR-induced cytotoxicity.

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“…miRNAs are increasingly recognized for their role in human mental illness (O'Connor et al ., ; Hauberg et al ., ). Single nucleotide polymorphisms associated with several miRNAs effect risk for anxiety disorders (Muinos‐Gimeno et al ., ; Hommers et al ., ), and expression levels of other miRNAs have been shown to correlate with anxiety symptoms (Xu et al ., ). Rodent studies show that acute and chronic stress affect miRNA expression (Meerson et al ., ; Rinaldi et al ., ), and rats that are vulnerable vs. resilient to developing learned helpless behaviour display baseline miRNA expression differences (Smalheiser et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

Cohen

Jackson

Ballestas

et al. 2017

Eur J of Neuroscience

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A greater understanding of neural mechanisms that contribute to anxiety is needed in order to develop better therapeutic interventions. The current study interrogates a novel molecular mechanism that shapes anxiety-like behavior, demonstrating that the microRNA miR-101a-3p and its target, enhancer of zeste homolog 2 (Ezh2) in the amygdala, contribute to rodent anxiety-like behavior. We utilized rats that were selectively-bred for differences in emotionality and stress reactivity, showing that high novelty responding (HR) rats, which display low trait anxiety, have lower miR-101a-3p levels in the amygdala compared to low novelty responding (LR) rats that characteristically display high trait anxiety. To determine if there is a causal relationship between amygdalar miR-101a-3p and anxiety behavior, we used a viral approach to over-express miR-101a-3p in the amygdala of HR rats and test whether it would increase their typically low levels of anxiety-like behavior. We found that increasing miR-101a-3p in the amygdala increased HRs’ anxiety-like behavior in the open field test and elevated plus maze. Viral-mediated miR-101a-3p over-expression also reduced expression of the histone methyltransferase Ezh2, which mediates gene silencing via tri-methylation of histone 3 at lysine 27 (H3K27me3). Knockdown of Ezh2 with short-interfering RNA (siRNA) also increased HRs’ anxiety-like behavior, but to a lesser degree than miR-101a-3p over-expression. Overall our data demonstrate that increasing miR-101a-3p expression in the amygdala increases anxiety-like behavior and that this effect is at least partially mediated via repression of Ezh2. This work adds to the growing body of evidence implicating miRNAs and epigenetic regulation as molecular mediators of anxiety behavior.

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Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing

Cited by 44 publications

References 35 publications

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

Microcystin-Leucine Arginine Causes Cytotoxic Effects in Sertoli Cells Resulting in Reproductive Dysfunction in Male Mice

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

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