LncARSR sponges miR-129-5p to promote proliferation and metastasis of bladder cancer cells through increasing SOX4 expression

International Journal of Biological Sciences, Journal Year: 2019, Volume and Issue: 16(1), P. 1 - 11

Published: Dec. 6, 2019

Emerging evidences have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers, playing important roles in the development of cancer. LncRNA Activated RCC with Sunitinib Resistance (lncARSR) is a novel lncRNA functions as biomarker and involved progression cancers. However, clinical significance molecular mechanism lncARSR bladder cancer (Bca) remains unknow. In this study, we discovered was significantly up-regulated addition, increased expression positively correlated higher histological grade larger tumor size. Further experiments demonstrated suppression attenuated proliferation, migration, invasion epithelial-mesenchymal transition (EMT) process Bca cells. Mechanistically, mainly located cytoplasm acted miRNA sponge to modulate Sex-determining region Y-related high-mobility-group box transcription factor 4 (SOX4) via sponging miR-129-5p subsequently promoted proliferation metastasis cells, thus an oncogenic role pathogenesis. conclusion, our study plays critical regulatory cells may serve diagnostic therapeutic target for

Language: Английский

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Downregulation of MEG3 promotes neuroblastoma development through FOXO1-mediated autophagy and mTOR-mediated epithelial-mesenchymal transition

International Journal of Biological Sciences, Journal Year: 2020, Volume and Issue: 16(15), P. 3050 - 3061

Published: Jan. 1, 2020

Our previous studies demonstrated that MEG3 was significantly downregulated in neuroblastoma (NB) and its expression negatively associated with the INSS stage. Overexpression of promoted apoptosis inhibited proliferation NB cells. In this study, we discovered more potential functions molecular mechanisms NB. According to database, positively correlated survival rate malignant clinical features. Moreover, determined mainly located nucleus by nuclear-cytoplasmic separation RNA fish assays. Upregulation stably transfected cell lines accomplished, CCK8, colony formation, EDU assays were performed, which indicated suppressed proliferation. Both wound healing transwell experiments decreased migration invasion. CHIRP enrichments showed anticancer effects probably linked autophagy mTOR signaling pathway. LC3 fluorescence dots western blots attenuated inhibiting FOXO1, but not Furthermore, metastasis through epithelial-mesenchymal transition via Consistent above results, downregulation facilitated phenotypes. Mechanistically, EZH2 regulated each other a negative feedback loop progression together. conclusion, our findings suggested tumor suppressor could be target for treatment future.

Language: Английский

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Lnc-PFAR facilitates autophagy and exacerbates pancreatic fibrosis by reducing pre-miR-141 maturation in chronic pancreatitis

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(11)

Published: Oct. 25, 2021

Abstract Chronic pancreatitis (CP) is described as progressive inflammatory fibrosis of pancreas, accompanied with irreversible impaired endocrine and exocrine insufficiency. Pancreatic stellate cells (PSCs) are widely distributed in the stroma pancreas PSCs activation has been shown one leading causes for pancreatic fibrosis. Our previous study revealed that autophagy dramatically activated CP tissues, which facilitates Long non-coding RNAs (LncRNAs) have recognized crucial regulators fibrosis-related diseases. LncRNAs interact RNA binding protein or construct competitive endogenous (ceRNA) hypothesis elicited fibrotic processes. Until now, effects lncRNAs on not clearly explored. In this study, a novel lncRNA named Lnc-PFAR was found highly expressed mouse human tissues. data via RB1CC1-induced autophagy. reduces miR-141 expression by suppressing pre-miR-141 maturation, eventually upregulates RB1CC1 indicators expression. Meanwhile, enhanced through trigging interrogates lncRNA-induced mechanism promoting development fibrosis, suggested to be prospective therapeutic target clinical scenarios.

Language: Английский

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Dysregulation of murine long noncoding single-cell transcriptome in nonalcoholic steatohepatitis and liver fibrosis

RNA, Journal Year: 2023, Volume and Issue: 29(7), P. 977 - 1006

Published: April 4, 2023

LncRNAs comprise a heterogeneous class of RNA-encoding genes typified by low expression, nuclear enrichment, high tissue-specificity, and functional diversity, but the vast majority remain uncharacterized. Here, we assembled mouse liver noncoding transcriptome from >2000 bulk RNA-seq samples discovered 48,261 liver-expressed lncRNAs, novel. Using these lncRNAs as single-cell transcriptomic reference set, elucidated lncRNA dysregulation in models fat diet-induced nonalcoholic steatohepatitis carbon tetrachloride-induced fibrosis. Trajectory inference analysis revealed zonation patterns across lobule each major cell population. Perturbations expression were common several disease-associated types, including steatohepatitis-associated macrophages, hallmark fatty disease progression, collagen-producing myofibroblasts, central feature Single-cell-based gene regulatory network using bigSCale2 linked individual to specific biological pathways, network-essential with functions identified their centrality metrics. For subset promoter sequences network-defined target significantly enriched for triplex formation, providing independent mechanistic support lncRNA–target linkages predicted networks. These findings elucidate cell-type specificities, spatial patterns, associated networks, temporal during hepatic progression. A have human orthologs are promising candidates biomarkers therapeutic targets.

Language: Английский

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Hepatocyte-derived exosomal miR-146a-5p inhibits hepatic stellate cell EMT process: a crosstalk between hepatocytes and hepatic stellate cells

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 19, 2023

Recently, Salidroside (Sal) has been demonstrated to suppress hepatic stellate cell (HSC) activation, a crucial event for liver fibrosis. Moreover, Sal reported decrease hepatocyte injury. A growing number of reports have indicated that the crosstalk between hepatocytes and HSCs is very fibrosis development. Whether Sal-treated could inhibit HSC activation unclear. Exosomes, as vital vehicles intercellular communication, shown transfer cargos HSCs. Herein, we aimed investigate roles exosomal miRNAs from in well Our results showed suppressed carbon tetrachloride (CCl4)-induced vivo. proliferation was repressed co-cultured with hepatocytes. Interestingly, miR-146a-5p up-regulated by CCl4-treated mice. Also, enhanced found isolated CCl4 mice hepatocyte-derived exosomes. Notably, contributed inactivation. Inhibiting exosomes resulted reduced E-cadherin (E-cad) increased desmin HSCs, indicating caused inactivation via epithelial-mesenchymal transition (EMT). inhibition-mediated EMT process were blocked down loss EIF5A2. Further studies revealed EIF5A2 target miR-146a-5p. Furthermore, overexpression inhibited Collectively, inhibits fibrosis, at least part, suppressing process.

Language: Английский

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