Non-coding RNA Research最新文献

Osteoporosis (OP)-associated fractures can result in severe morbidity and disability, reduced quality of life, and death. Previous studies have suggested that small noncoding RNAs, for example, small regulatory microRNAs (miRNAs), play a key role in OP by inhibiting target gene expression. Cuproptosis, a recently proposed copper-induced cell death pathway, is linked with OP. Here, we describe the contribution of exosomal miRNAs and cuproptosis to OP. First, we highlight the characteristics of exosomes and roles of exosome-related miRNAs. Next, we discuss the relationship between cuproptosis and OP. Subsequently, we analyze the crosstalk of exosomal miRNAs with cuproptosis in the development of OP. This review aims to investigate a new clinical treatment method for OP.

Myeloid-derived suppressor cells (MDSCs) are closely related to the occurrence and development of many cancers, but the specific mechanism is not fully understood. It has been found that N6-methyladenosine (m⁶A) plays a key role in RNA metabolism, but its function in MDSCs has yet to be revealed. In this study, we found that MDSCs in mice with colorectal cancer (CRC) have significantly elevated levels of m⁶A, while ALKBH5 expression is decreased. Overexpression of ALKBH5 can reduce the immunosuppressive function of MDSCs in vivo and in vitro, and attenuates the protumorigenic ability of MDSCs. Mechanism study found that the overexpression of ALKBH5 in MDSCs reduced the m⁶A modification level of Arg-1 mRNA, and then weakened the stability of Arg-1 mRNA and protein expression. These data suggest that the decreased expression of ALKBH5 in CRC tumor mice may promote the expression of Arg-1, enhance the immunosuppressor function of MDSCs, and promote tumor growth. These findings highlight that ALKBH5 may regulate the function of MDSCs in tumor-bearing mice and may be a new target for immunotherapy. This research provides a new perspective for our understanding of the role of MDSCs in cancer development, and also brings new hope for cancer treatment.

Colorectal cancer (CRC) incidence ranks third among malignant cancers with a high propensity for distant metastasis. Despite continuous efforts to improve treatment, the prognosis especially in patients with advanced distant metastasis is low. The mechanism of development and progression of CRC is not fully understood. Non-coding RNAs (ncRNAs) have emerged as essential regulators in cancer progression. Here, we aim to dissect the role of one critical ncRNA, circANXA4, in CRC progression. CircANXA4 expression was analyzed by the GEO database. Differentially expressed circRNAs were identified by the Limma package R software. Expression of circANXA4 and miR-1256 was detected by qRT-PCR. The regulation of circANXA4 on cell proliferation and progression was confirmed with the cell viability assay using cell counting kit-8 (CCK-8) and transwell migration assay. RNA pull-down assay, RNA immunoprecipitation (RIP), and western blot were used to determine the interaction between circANXA4, miR-1256, and protamine1 (PRM1). CircANXA4 was upregulated in both CRC tissues and cell lines. Knockdown of circANXA4 effectively reduced cell proliferation, progression, and migration. Additionally, silencing circANXA4 remarkably increased miR-1256 expression, while reducing PRM1 expression, thereby demonstrating that circANXA4 downregulates miR-1256 expression through a complementary binding site. Rescue experiments revealed the interactions between circANXA4, miR-1256, and PRM1. Pearson correlation analysis revealed that circANXA4 expression positively correlated with PRM1 expression and miR-1256 expression inversely correlated with PRM1 expression. In sum, we demonstrated that circANXA4 promotes cancer cell proliferation and progression by sponging miR-1256 and upregulating PRM1 in CRC.

Background

Hypersensitivity pneumonitis (HP) is an inflammatory disorder affecting lung parenchyma and often evolves into fibrosis (fHP). The altered regulation of genes involved in the pathogenesis of the disease is not well comprehended, while the role of microRNAs in lung fibroblasts remains unexplored.

Methods

We used integrated bulk RNA-Seq and enrichment pathway bioinformatic analyses to identify differentially expressed (DE)-miRNAs and genes (DEGs) associated with HP lungs. In vitro, we evaluated the expression and potential role of miR-155-5p in the phenotype of fHP lung fibroblasts. Loss and gain assays were used to demonstrate the impact of miR-155-5p on fibroblast functions. In addition, mir-155-5p and its target TP53INP1 were analyzed after treatment with TGF-β, IL-4, and IL-17A.

Results

We found around 50 DEGs shared by several databases that differentiate HP from control and IPF lungs, constituting a unique HP lung transcriptional signature. Additionally, we reveal 18 DE-miRNAs that may regulate these DEGs. Among the candidates likely associated with HP pathogenesis was miR-155-5p. Our findings indicate that increased miR-155-5p in fHP fibroblasts coincides with reduced TP53INP1 expression, high proliferative capacity, and a lack of senescence markers compared to IPF fibroblasts. Induced overexpression of miR-155-5p in normal fibroblasts remarkably increases the proliferation rate and decreases TP53INP1 expression. Conversely, miR-155-5p inhibition reduces proliferation and increases senescence markers. TGF-β, IL-4, and IL-17A stimulated miR-155-5p overexpression in HP lung fibroblasts.

Conclusion

Our findings suggest a distinctive signature of 53 DEGs in HP, including CLDN18, EEF2, CXCL9, PLA2G2D, and ZNF683, as potential targets for future studies. Likewise, 18 miRNAs, including miR-155-5p, could be helpful to establish differences between these two pathologies. The overexpression of miR-155-5p and downregulation of TP53INP1 in fHP lung fibroblasts may be involved in his proliferative and profibrotic phenotype. These findings may help differentiate and characterize their pathogenic features and understand their role in the disease.

Background

Individuals with homozygous familial hypercholesterolemia (HoFH) have a severe clinical problem in their first decade of life, which is not usually present in heterozygous FH (HeFH) individuals. For this latter group of patients, FH diagnosis is mostly severely delayed with a significant increase in the risk of angina, myocardial infarction, peripheral artery disease, stroke, and cardiovascular and all-cause mortality.

Methods

This study used various bioinformatics tools to analyze microarray data and identify critical miRNAs and their target genes associated with FH and its severity. Differentially expressed serum miRNAs from direct hybridization microarray data in three groups of subjects: healthy, HeFH, and HoFH. The differential expressed miRNAs were determined according to a log of fold-change (LFC) <-0.5 or >0.5 and of p < 0.05. Then, we assessed their target genes in silico. Gene ontology (GO) enrichment was applied by Cytoscape. The protein-protein interaction and co-expression network were analyzed by the STRING and GeneMANIA plugins of Cytoscape, respectively.

Results

We identified increased expression of circulating hsa-miR-604, hsa-miR-652-5p, and hsa-miR-4451 as well as reduced expression of hsa-miR-3140-3p, hsa-miR-550a-5p, and hsa-miR-363-3p in both group of FH vs. healthy subjects. Higher levels of hsa-miR-1183, hsa-miR-1185-1-3p, hsa-miR-122-5p, hsa-miR-19a-3p, hsa-miR-345-3p, and hsa-miR-34c-5p were detected in HeFH in respect to HoFH when compared to healthy subjects. Most upregulated miRNAs mainly affected gene related to cardiac myofibrillogenesis, cholesterol synthesis, RNA editing for apolipoprotein B, and associated with LDL-cholesterol levels. In contrast, down-regulated miRNAs mainly affected gene related to plasma biomarker for coronary artery disease, lipids metabolism, cell adhesion and migration, genetic predictors of type 2 diabetes and cholesterol metabolism. The essential genes were primarily enriched in GO regarding biological regulation, intracellular nucleic acid binding, and the KEGG pathway of TGF-β signaling.

Conclusions

The case-control nature of this study precluded the possibility of assessing the predictive role of the identified differentially expressed miRNAs for cardiovascular events. Therefore, the signature of miRNAs reflecting the pathogenesis of both HeFH and HoFH.

Hypoxia is a critical feature of solid tumors and exerts crucial roles in cancers, including breast cancer. However, the detailed relationship between lncRNA-miRNA-mRNA triple network and hypoxia in breast cancer is still indistinct. In this study, a series of in silico analyses and online databases or tools were employed to establish a hypoxia-related lncRNA-miRNA-mRNA network in breast cancer based on competing endogenous RNA mechanism at single-cell resolution. RAMP2-AS1 was, eventually, identified as the most potential lncRNA, which was significantly negatively associated with hypoxia in breast cancer. Compared with normal controls, RAMP2-AS1 was markedly downregulated in breast cancer. Moreover, survival analysis revealed favorable prognostic values of RAMP2-AS1 in total or in specific clinicopathological breast cancer patients. Next, miR-660-5p, miR-2277-5p and miR-1301-3p, upregulated and possessed poor prognostic values in breast cancer, were identified as three potential downstream miRNAs of RAMP2-AS1. Then, the most potential downstream hypoxia-related genes (ATM and MYH11) of RAMP2-AS1/miRNA axis in breast cancer were screened out. Intriguingly, in vitro experiments confirmed that RAMP2-AS1 was a hypoxia-suppressed lncRNA and miR-660-5p/ATM was a potential downstream axis of RAMP2-AS1 in breast cancer. Collectively, our current data elucidated a key hypoxia-suppressed lncRNA RAMP2-AS1 and its possible miRNA-mRNA regulatory mechanism in breast cancer.

Hirschsprung's disease (HSCR) is a congenital disorder characterized by the absence of ganglion cells in the colon, leading to various intestinal complications. The etiology of HSCR stems from complex genetic and environmental interactions, of which the intricate roles of non-coding RNAs (ncRNAs) are a key area of research. However, the roles of ncRNAs in the pathogenesis of HSCR have not been fully elucidated. In order to understand the variety of symptoms caused by HSCR and develop new therapeutic approaches, it is essential to understand the underlying biological genetic basis of HSCR. This review presents a comprehensive overview of the current understanding regarding the involvement of ncRNAs in HSCR, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Additionally, it provides a summary of the molecular mechanisms through which ncRNAs regulate the expression of genes related to the proliferation, migration, and differentiation of intestinal neural crest cells, thereby contributing to the advancement of HSCR research.

Background

In cervical cancer (CC), miR-218-5p, -124-3p, and −23b-3p act as tumor suppressors. These miRNAs have specific and common target genes that modulate apoptosis, proliferation, invasion, and migration; biological processes involved in cancer.

Methods

miR-218-5p, -124-3p, and −23b-3p mimics were transfected into C-33A and CaSki cells, and RT-qPCR was used to quantify the level of each miRNA and NACC1. Proliferation was assessed by BrdU and apoptosis by Annexin V/PI. In the TCGA and The Human Protein Atlas databases, the level of NACC1 mRNA and protein (putative target of the three miRNAs) was analyzed in CC and normal tissue. The relationship of NACC1 with the overall survival in CC was analyzed in GEPIA2. NACC1 mRNA and protein levels were higher in CC tissues compared with cervical tissue without injury.

Results

An increased expression of NACC1 was associated with lower overall survival in CC patients. The levels of miR-218-5p, -124-3p, and −23b-3p were lower, and NACC1 was higher in C-33A and CaSki cells compared to HaCaT cells. The increase of miR-218-5p, -124-3p, and −23b-3p induced a significant decrease in NACC1 mRNA. The transfection of the three miRNAs together caused more drastic changes in the level of NACC1, in the proliferation, and in the apoptosis with respect to the individual transfections of each miRNA.

Conclusion

The results indicate that miR-218-5p, -124-3p, and −23b-3p act synergistically to decrease NACC1 expression and proliferation while promoting apoptosis in C-33A and CaSki cells. The levels of NACC1, miR-218-5p, -124-3p, and −23b-3p may be a potential prognostic indicator in CC.