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Hsa_circ_0008537 facilitates liver carcinogenesis by upregulating MCL1 and Snail1 expression via miR‑153‑3p.
Yang, G, Li, X, Liu, J, Huang, S, Weng, Y, Zhu, J, Lin, D, Jiang, O
Oncology reports. 2021;(3):1072-1082
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Abstract
The biological functions of circular RNAs in liver tumorigenesis have been well demonstrated by a number of studies. Nevertheless, to the best of our knowledge, the role and mechanism of action of hsa_circ_0008537 (circ_0008537) in liver cancer pathogenesis remain undetermined. In the present study, circ_0008537 expression was associated with the GLI3 gene and was markedly increased in liver cancer tissue specimens and cells. High expression levels of circ_0008537 exhibited a poor prognosis. In addition, circ_0008537 overexpression resulted in an increased proliferation, migration and invasion of liver cancer cells, whereas circ_0008537 knockdown exhibited opposite effects. circ_0008537 acted as a sponge of microRNA‑153‑3p (miR‑153‑3p), and a negative correlation was observed between circ_0008537 and miR‑153‑3p expression in liver cancer. Transfection with miR‑153‑3p further abolished the effects of circ_0008537 on the malignant behavior of liver cancer cells. Furthermore, circ_0008537 indirectly affected the expression levels of pro‑survival protein myeloid cell leukemia 1 (MCL1) and snail family zinc finger 1 (Snail1) via miR‑153‑3p in liver cancer cells. In conclusion, the data indicated that circ_0008537 facilitated liver carcinogenesis by indirectly regulating miR‑153‑3p and leading to the release of MCL1 and Snail1.
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Integration of sRNA, degradome, transcriptome analysis and functional investigation reveals gma-miR398c negatively regulates drought tolerance via GmCSDs and GmCCS in transgenic Arabidopsis and soybean.
Zhou, Y, Liu, W, Li, X, Sun, D, Xu, K, Feng, C, Kue Foka, IC, Ketehouli, T, Gao, H, Wang, N, et al
BMC plant biology. 2020;(1):190
Abstract
BACKGROUND Drought conditions adversely affect soybean growth, resulting in severe yield losses worldwide. Increasing experimental evidence indicates miRNAs are important post-transcriptional regulators of gene expression. However, the drought-responsive molecular mechanism underlying miRNA-mRNA interactions remains largely uncharacterized in soybean. Meanwhile, the miRNA-regulated drought response pathways based on multi-omics approaches remain elusive. RESULTS We combined sRNA, transcriptome and degradome sequencing to elucidate the complex regulatory mechanism mediating soybean drought resistance. One-thousand transcripts from 384 target genes of 365 miRNAs, which were enriched in the peroxisome, were validated by degradome-seq. An integrated analysis showed 42 miRNA-target pairs exhibited inversely related expression profiles. Among these pairs, a strong induction of gma-miR398c as a major gene negatively regulates multiple peroxisome-related genes (GmCSD1a/b, GmCSD2a/b/c and GmCCS). Meanwhile, we detected that alternative splicing of GmCSD1a/b might affect soybean drought tolerance by bypassing gma-miR398c regulation. Overexpressing gma-miR398c in Arabidopsis thaliana L. resulted in decreased percentage germination, increased leaf water loss, and reduced survival under water deficiency, which displayed sensitivity to drought during seed germination and seedling growth. Furthermore, overexpressing gma-miR398c in soybean decreased GmCSD1a/b, GmCSD2a/b/c and GmCCS expression, which weakened the ability to scavenge O2.-, resulting in increased relative electrolyte leakage and stomatal opening compared with knockout miR398c and wild-type soybean under drought conditions. CONCLUSION The study indicates that gma-miR398c negatively regulates soybean drought tolerance, and provides novel insights useful for breeding programs to improve drought resistance by CRISPR technology.
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lncRNA FEZF1‑AS1 promotes migration, invasion and epithelial‑mesenchymal transition of retinoblastoma cells by targeting miR‑1236‑3p.
Zhang, G, Yang, W, Li, D, Li, X, Huang, J, Huang, R, Luo, J
Molecular medicine reports. 2020;(5):3635-3644
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Abstract
Long non‑coding RNAs (lncRNAs) and microRNAs (miRs) have been reported to regulate disease progression in numerous types of disease, including retinoblastoma (Rb). Therefore, the present study aimed to investigate the effects of the lncRNA FEZ family zinc finger 1 antisense RNA 1 (FEZF1‑AS1) on Rb and to determine its possible mechanism of action. Reverse transcription‑quantitative PCR and western blot analysis were conducted to detect the gene or protein expression. Cell Counting Kit‑8, wound healing and transwell invasion assays were performed to estimate the capabilities of cell viability, invasion and migration. The potential association between FEZF1‑AS1 and miR‑1236‑3p in Y79 cells was measured via dual‑luciferase reporter assay. The results of the present study revealed that the levels of FEZF1‑AS1 were significantly upregulated in different Rb cell lines, with the most prominent upregulation observed in Y79 cells. In addition, the cell viability, invasive and migratory abilities, and the ability to undergo epithelial‑mesenchymal transition (EMT), were significantly inhibited following the transfection of short hairpin RNA (shRNA)‑FEZF1‑AS1 into Y79 cells. Further experimental validation confirmed that miR‑1236‑3p may be a direct target of FEZF1‑AS1. Notably, the miR‑1236‑3p inhibitor was discovered to reverse the inhibitory effects of shRNA‑FEZF1‑AS1 on cell viability, invasion, migration and EMT. In conclusion, the findings of the present study suggested that lncRNA‑FEZF1‑AS1 may promote the viability, migration, invasion and EMT of Rb cells by modulating miR‑1236‑3p.
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Circulating miR-30d Predicts Survival in Patients with Acute Heart Failure.
Xiao, J, Gao, R, Bei, Y, Zhou, Q, Zhou, Y, Zhang, H, Jin, M, Wei, S, Wang, K, Xu, X, et al
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017;(3):865-874
Abstract
BACKGROUND/AIMS: Identification of novel biomarkers to identify acute heart failure (AHF) patients at high risk of mortality is an area of unmet clinical need. Recently, we reported that the baseline level of circulating miR-30d was associated with left ventricular remodeling in response to cardiac resynchronization therapy in advanced chronic heart failure patients. However, the role of circulating miR-30d as a prognostic marker of survival in patients with AHF has not been explored. METHODS Patients clinically diagnosed with AHF were enrolled and followed up for 1 year. Quantitative reverse transcription polymerase chain reactions were used to determine serum miR-30d levels. The univariate logistic regression analysis and multivariate logistic regression analysis were used to determine the predictors for all-cause mortality in AHF patients. Kaplan-Meier survival analysis was used to analyze the role of miR-30d in prediction of survival. RESULTS A total of 96 AHF patients were enrolled and followed up for 1 year. Serum miR-30d was significantly lower in AHF patients who expired in the one year follow-up period compared to those who survived. Univariate logistic regression analysis yielded 18 variables that were associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 4 variables including heart rate, hemoglobin, serum sodium, and serum miR-30d level associated with mortality. ROC curve analysis showed that hemoglobin, heart rate and serum sodium displayed poor prognostic value for AHF (AUCs not higher than 0.700) compared to miR-30d level (AUC = 0.806). Kaplan-Meier survival analysis confirmed that patients with higher serum miR-30d levels had significantly lower mortality (P=0.001). CONCLUSION In conclusion, this study shows evidence for the predictive value of circulating miR-30d as 1-year all-cause mortality in AHF patients. Large multicentre studies are further needed to validate our findings and accelerate the transition to clinical utilization.