An integrated analysis of the circRNA–miRNA–mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration

Wang, Gaiping; Guo, Xueqiang; Cheng, Lijun; Chu, Peipei; Meng, Chen; Chen, Yanhui; Chang, Cuifang

doi:10.1080/21691401.2019.1669623

Cited by 24 publications

(17 citation statements)

References 57 publications

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“…The competitive endogenous RNA (ceRNA) hypothesis is a new model for post transcriptional gene regulation. According to the hypothesis, the expressions of designated miRNAs are reduced by ceRNA [ 39 ]. Nowadays, a lot of evidence has attested that the form circRNA–miRNA–mRNA is important to explore the pathogenesis of tumors and other diseases.…”

Section: Discussionmentioning

confidence: 99%

CircRNA-006258 Sponge-Adsorbs miR-574-5p to Regulate Cell Growth and Milk Synthesis via EVI5L in Goat Mammary Epithelial Cells

Zhang

Liu

et al. 2020

Genes

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The development of the udder and the milk yield are closely related to the number and vitality of mammary epithelial cells. Many previous studies have proved that non-coding RNAs (ncRNAs) are widely involved in mammary gland development and the physiological activities of lactation. Our laboratory previous sequencing data revealed that miR-574-5p was differentially expressed during the colostrum and peak lactation stages, while the molecular mechanism of the regulatory effect of miR-574-5p on goat mammary epithelial cells (GMECs) is unclear. In this study, the targeting relationship was detected between miR-574-5p or ecotropic viral integration site 5-like (EVI5L) and circRNA-006258. The results declared that miR-574-5p induced the down-regulation of EVI5L expression at both the mRNA and protein levels, while circRNA-006258 relieved the inhibitory effect through adsorbing miR-574-5p. EVI5L blocked the G1 phase and promoted the S phase by activating the Rab23/ITGB1/TIAM1/Rac1-TGF-β/Smad pathway in GMECs. By increasing the protein expression of Bcl2 and reducing the protein expression of Bax, EVI5L promoted cell growth and inhibited apoptosis. The activation of the PI3K/AKT–mTOR signaling pathway promoted the production of triacylglycerol (TAG) and β-casein in GMECs. The circRNA–006258/miR-574-5p/EVI5L axis could regulate the cell growth and milk synthesis of GMECs by sponge-adsorbed miR-574-5p. These results would provide scientific evidence for precision animal breeding in the industry of dairy goats.

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Section: Discussionmentioning

confidence: 99%

CircRNA-006258 Sponge-Adsorbs miR-574-5p to Regulate Cell Growth and Milk Synthesis via EVI5L in Goat Mammary Epithelial Cells

Zhang

Liu

et al. 2020

Genes

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“…In addition, our further research showed that EPS1-1 regulated the expression of oncogenes and tumor suppressor genes, thereby through which might exert its biological function. These genes include cell proliferation promoting factors including CCND1 and c-Myc (Wang G. et al, 2019;Zhang D. et al, 2019), cell apoptosis regulators BAX and Bcl-2 (Zhang Q. et al, 2019;Hu et al, 2020), and factors that promote cell migration and invasion, such as Vimentin and Slug (Lillo Osuna et al, 2019;Shahid et al, 2019). Study by Song et al (2019) showed that EPS1-1 could reduce the expression of oncoproteins such as COX-2, β-catenin, CyclinD1, and C-Myc, and down-regulate the expression of proliferation-related proteins including Ki-67 and PCNA and the anti-apoptotic gene Bcl-2, up-regulate the expression of pro-apoptotic genes such as p53 and Bax, reduce the number of CD68, F4/80, and NF-κB positive cells, as well as reducing the concentrations of inflammatory factors in serum including TNF-α and IL-6.…”

Section: Discussionmentioning

confidence: 99%

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

Chu

Miao

Huang

et al. 2020

Front. Bioeng. Biotechnol.

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Objective: This work is to study the effect of Rhizopus nigrum polysaccharide EPS1-1 on hepatocellular carcinoma (HCC) in vitro and in vivo. Methods: HepG2 and Huh-7 cells and nude mice models of liver cancers were used in this study. The cells and nude mice were treated with EPS1-1 at different concentrations. The CCK8 assays were used to measure the proliferation activities of cells, apoptosis was determined with flow cytometry, cell migration was measured by wound-healing assays, cell invasion was evaluated by Transwell assay, and the survival periods of different groups of tumor-bearing mice were compared. Real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins of the genes related to proliferation, apoptosis, migration, and invasion. Results: In vitro experiments revealed that when treated with EPS1-1, HepG2 and Huh-7 cell proliferation activities decreased, while there was an increase for the apoptosis rate, and the migration and invasion capabilities were significantly reduced. In vivo experiments showed that EPS1-1 could significantly reduce the tumor growth and lung metastasis of HCC, and prolong the survival periods of tumor-bearing nude mice. Furthermore, EPS1-1 has no apparent damage to the heart, liver, and kidney. Further studies showed that EPS1-1 could affect the expression of proliferation-related genes CCND1 and c-Myc, apoptosis-related genes BAX and Bcl-2, and migration and invasion related genes Vimentin and Slug, thereby affecting the biological process of HCC. Conclusion: EPS1-1 can inhibit the malignant process of HCC in vitro and in vivo, which indicates that EPS1-1 has the potential value of clinical application as chemotherapy or adjuvant in the treatment of liver cancer.

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“…In particular, the importance of the ceRNA mechanism is related to its capacity to offer new indications for diagnostic and prognostic putative biomarkers [ 94 , 189 ], targets for drugs such as in hypertrophic scars treatment [ 190 ] and predictions for therapeutic strategies, such as in the cell proliferation of complex mechanisms in regenerating livers [ 87 , 178 ], or as in the broad spectrum of tumors [ 191 , 192 , 193 , 194 ] or still as in the pathogenesis of early HIV infection and its related antiviral therapy [ 165 ].…”

Section: Discussionmentioning

confidence: 99%

“…Instances of ceRNA crosstalk were experimentally tested in a very large number of contexts and were observed in both normal and pathological backgrounds, demonstrating the wide spread proliferation of the mechanism. In particular, researchers collected evidence from normal physiology, for instance in brain architecture [ 86 ] and regeneration mechanisms [ 87 ], neuronal and muscle developmental processes [ 50 , 88 ], cellular differentiation [ 89 ] and reprogramming [ 90 , 91 ] and from the immense landscape of diseases, syndromes and disorders where highly complex gene regulation circuits are most affected by perturbations. Researchers work hard to model these regulatory networks in order to predict and understand how modifications could alter the dynamic balance among molecules, causing illness such as the onset of cancer and its progression, cardiovascular problems and neurodegenerative disorders and other pathologies, such as those relating to the immune and autoimmune response and to degenerative physical condition.…”

Section: Cerna and Diseasesmentioning

confidence: 99%

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

Ala

2020

Cells

103

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MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are responsible for RNA silencing and post-transcriptional regulation of gene expression. They can mediate a fine-tuned crosstalk among coding and non-coding RNA molecules sharing miRNA response elements (MREs). In a suitable environment, both coding and non-coding RNA molecules can be targeted by the same miRNAs and can indirectly regulate each other by competing for them. These RNAs, otherwise known as competing endogenous RNAs (ceRNAs), lead to an additional post-transcriptional regulatory layer, where non-coding RNAs can find new significance. The miRNA-mediated interplay among different types of RNA molecules has been observed in many different contexts. The analyses of ceRNA networks in cancer and other pathologies, as well as in other physiological conditions, provide new opportunities for interpreting omics data for the field of personalized medicine. The development of novel computational tools, providing putative predictions of ceRNA interactions, is a rapidly growing field of interest. In this review, I discuss and present the current knowledge of the ceRNA mechanism and its implications in a broad spectrum of different pathologies, such as cardiovascular or autoimmune diseases, cancers and neurodegenerative disorders.

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An integrated analysis of the circRNA–miRNA–mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration

Abstract: Chang (2019) An integrated analysis of the circRNA-miRNA-mRNA network reveals novel insights into potential mechanisms of cell proliferation during liver regeneration,

Cited by 24 publications

References 57 publications

CircRNA-006258 Sponge-Adsorbs miR-574-5p to Regulate Cell Growth and Milk Synthesis via EVI5L in Goat Mammary Epithelial Cells

CircRNA-006258 Sponge-Adsorbs miR-574-5p to Regulate Cell Growth and Milk Synthesis via EVI5L in Goat Mammary Epithelial Cells

Role and Mechanism of Rhizopus Nigrum Polysaccharide EPS1-1 as Pharmaceutical for Therapy of Hepatocellular Carcinoma

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

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