Circular RNA hsa_circ_0005519 contributes to acute kidney injury via sponging microRNA-98-5p
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ABSTRACT:
SUBMITTER: Jiang L
PROVIDER: S-EPMC10949765 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Recently, several studies have been conducted on circRNA (circular RNA). circRNA regulates gene expression and plays a vital role in the occurrence and development of various tumors. However, the role and mechanism of hsa_circ_0032683 in hepatocellular carcinoma (HCC) is not studied yet. In GEO (Gene Expression Omnibus) database, hsa_circ_0032683 expression was significantly lower in HCC tissues than in normal liver tissues. In vitro and in vivo functional tests revealed that hsa_circ_0032683 could inhibit HCC cells proliferation and promote their apoptosis. Mechanically, hsa_circ_0032683 primarily exists in the cytoplasm and competes with microRNA-338-5p (miR-338-5p) to regulate reticulon 4(RTN4). Our experiments revealed that hsa_circ_0032683 receded the proliferation ability of HCC via ceRNA (competing endogenous RNAs) mechanism, which provided potential biomarkers and therapeutic targets for HCC patients.Abbreviations: circRNAs: circular RNA; HCC: hepatocellular carcinoma; RTN4: reticulon 4; ceRNA: competing endogenous RNA; GEO: Gene Expression Omnibus; miRNA: microRNA; CSCD: Cancer-specific circRNA database; CRI: Circular RNA Interactome; TCGA: The Cancer Genome Atlas; qRT-PCR: quantitative real-time PCR; NEK9:NIMA-related kinase nine; CSMD1: CUB and Sushi multiple domains 1; Tob1: transducer of ERBB2, 1; miR: microRNA; sh: short hairpin; WT: wild type; MUT: mutant.
| S-EPMC8974012 | biostudies-literature
Project description:BackgroundRenal ischemia-reperfusion (I/R) injury is a major cause of AKI. Noncoding RNAs are intricately involved in the pathophysiology of this form of AKI. Transcription of hypoxia-induced, long noncoding RNA H19, which shows high embryonic expression and is silenced in adults, is upregulated in renal I/R injury.MethodsLentivirus-mediated overexpression, as well as antisense oligonucleotide-based silencing, modulated H19 in vitro. In vivo analyses used constitutive H19 knockout mice. In addition, renal vein injection of adeno-associated virus 2 (AAV2) carrying H19 caused overexpression in the kidney. Expression of H19 in kidney transplant patients with I/R injury was investigated.ResultsH19 is upregulated in kidney biopsies of patients with AKI, in murine ischemic kidney tissue, and in cultured and ex vivo sorted hypoxic endothelial cells (ECs) and tubular epithelial cells (TECs). Transcription factors hypoxia-inducible factor 1-α, LHX8, and SPI1 activate H19 in ECs and TECs. H19 overexpression promotes angiogenesis in vitro and in vivo. In vivo, transient AAV2-mediated H19 overexpression significantly improved kidney function, reduced apoptosis, and reduced inflammation, as well as preserving capillary density and tubular epithelial integrity. Sponging of miR-30a-5p mediated the effects, which, in turn, led to target regulation of Dll4, ATG5, and Snai1.ConclusionsH19 overexpression confers protection against renal injury by stimulating proangiogenic signaling. H19 overexpression may be a promising future therapeutic option in the treatment of patients with ischemic AKI.
| S-EPMC8054899 | biostudies-literature
Project description:Bladder cancer (BC) is the most frequent type of urinary tumor and a barely treatable disease. Although extensive efforts have been invested in the research of BC, the underlying etiology and pathophysiology remain unclear. CircLONP2 is a circular RNA implicated in the development of many cancers, and miR-584-5p and YAP1 have been reported to contribute to the progression of BC. In this research, we presented novel evidence supporting circLONP2/miR-584-5p/YAP1 axis as a novel regulatory module in the progression of BC. We analyzed the expression of circLONP2 between precancerous BC samples and normal tissues using a published RNA-seq dataset. The expression of circLONP2 was also validated in clinical samples and cell lines by quantitative RT-PCR. Small interfering RNA (siRNA) and miRNA inhibitor was utilized to modulate the expression of circLONP2 and miR-584-5p and investigate their functions on cell proliferation and invasion. Luciferase reporter assay and RNA pull-down were performed to confirm the functional interactions among circLONP2/miR-584-5p/YAP1. CircLONP2 was significantly upregulated in precancerous BC tissues and BC cells. CircLONP2 depletion inhibited cell viability, proliferation, and invasion of BC cell lines, which could be partially rescued by miR-584-5p inhibitor. Further experiments indicated that miR-584-5p regulates cell viability, proliferation, and invasion via directly targeting YAP1. In summary, our work indicates that circLONP2 plays an oncogenic function in BC by regulating miR-584-5p/YAP1 axis, and its interaction with miR-584-5p provides a potential strategy to target BC.
| S-EPMC9161836 | biostudies-literature
Project description:BackgroundLaryngeal squamous cell carcinoma (LSCC) belongs to tumors of head and neck. Circular RNA circSLC7A11 functions as oncogenes in various tumors. However, the role of circSLC7A11 in LSCC remains largely unknown. Here, we aimed to clarify the circSLC7A11 function in LSCC.MethodsRelevance between circSLC7A11 expressions and LSCC clinicopathological was checked using chi-square. Relevance between circSLC7A11 expressions and LSCC patients' survival time was validated using Kaplan-Meier analysis. CircSLC7A11 expressions in LSCC tissues and cells were determined using quantitative real-time PCR. CircSLC7A11 functions in LSCC were examined by Cell Counting Kit-8, EdU analysis, Western blot, flow cytometry, sphere formation assay, and Transwell analysis. Meanwhile, circSLC7A11 mechanism in LSCC was determined using dual-luciferase reporter analysis, RNA pull-down, RNA Immunoprecipitation.ResultsCircSLC7A11 was highly expressed in LSCC, and high circSLC7A11 expressions were interrelated to the TNM stage. Also, LSCC patients with high circSLC7A11 owned shorter overall survival. Functional studies revealed that circSLC7A11 knockdown reduced LSCC cell proliferation, migration, invasion, stemness characteristics, and enhanced cell apoptosis. Mechanistic study data corroborated that circSLC7A11 targeted miR-877-5p, miR-877-5p targeted LASP1. LASP1 was negatively interrelated to miR-877-5p and was positively interrelated to circSLC7A11 in LSCC tissues. Also, circSLC7A11 knockdown reduced the LASP1 levels, and miR-877-5p inhibitor co-transfection reversed this reduction. Rescue assays further demonstrated that circSLC7A11 accelerated LSCC through miR-877-5p/LASP1.ConclusionCircSLC7A11 exerted oncogenic functions in LSCC by miR-877-5p/LASP1, hinting that circSLC7A11 was a novel biomarker for LSCC.
| S-EPMC10393633 | biostudies-literature
Project description:Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. CircZNF609 was found to be involved in hepatocellular carcinoma, but the role and underlying mechanism of circZNF609 in laryngeal squamous cell carcinoma (LSCC) remain unclear. This study aimed to explore the molecular mechanism of circZNF609 in LSCC. qRT-qPCR was performed to detect the expression of circZNF609 and microRNA-134-5p (miR-134-5p) in LSCC. Colony formation assay, CCK-8 assay, BrdU incorporation assay, clone formation assay, transwell invasion assay and Western blot analysis were performed to evaluate LSCC cell proliferation, as well as the expression of proliferating cell nuclear antigen (PCNA) and MMP-2. Luciferase reporter assay, target gene prediction and screening were used to validate downstream target genes of circZNF609 and miR-134-5p. EGFR expression was detected by Western blot analysis and RT-qPCR. Nude mice were used to detect tumor changes. CircZNF609 was upregulated in LSCC and associated with poor survival of LSCC patients. Knockdown of circZNF609 inhibited LSCC proliferation, invasion and the expression of PCNA and matrix matalloproteinases-2 (MMP-2). CircZNF609 can regulate miR-134-5p to upregulate epidermal growth factor receptor (EGFR). In addition, knockdown of EGFR or overexpression of miR-134-5p could reverse the tumor-promoting effects of circZNF609 in LSCC. In LSCC tissues, circZNF609 was negatively correlated with miR-134-5p and positively correlated with EGFR. CircZNF609 promotes the progression of LSCC via the miR-134-5p/EGFR axis, which might be the therapeutic target of LSCC.
| S-EPMC8973624 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are considered as key regulators of cancer biology. Recently, cMTO1 (a circRNA derived from MTO1 gene, hsa_circ_0007874) has been demonstrated to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the roles of cMTO1 in liver fibrosis are largely unknown.MethodsExpressions and roles of cMTO1 were examined in vivo and in vitro during liver fibrosis. The interaction between microRNA-181b-5p (miR-181b-5p) and cMTO1 was analyzed by luciferase activity assays and pull down assays.ResultscMTO1 was shown to be reduced in the liver from patients with cirrhosis. In addition, cMTO1 was down-regulated in the mouse fibrotic livers as well as activated hepatic stellate cells (HSCs). Restoring of cMTO1 led to a reduction in HSC proliferation. Results of immunofluorescence analysis showed that cMTO1 suppressed the expressions of α-SMA and type I collagen. cMTO1 was found to be expressed in the cytoplasm of HSCs. Further studies confirmed that cMTO1 and miR-181b-5p were co-located in the cytoplasm. Interestingly, there was an interaction between cMTO1 and miR-181b-5p. Results of luciferase reporter assays and pull down assays confirmed that miR-181b-5p could bind to cMTO1. cMTO1-inhibited HSC activation was blocked down by miR-181b-5p or PTEN. Meanwhile, PTEN was a target of miR-181b-5p.ConclusioncMTO1 inhibits HSC activation, at least in part, through miR-181b-5p-mediated PTEN expression. Our results also suggest that cMTO1 may be a novel therapeutic target in liver fibrosis.
| S-EPMC7413143 | biostudies-literature
Project description:CircRNAs have critical effects on tumor development and progression. However, circPGD effect on gastric cancer (GC) is still elusive. Nuclear and cytoplasmic RNA fractionation, and RNA-FISH assay examined the localization of circPGD in MGC-803 cells. qRT-PCR was conducted to detect the expression and prognostic significance of circPGD, miR-16-5p, and ABL2 within GC tissues. Meanwhile, qRT-PCR, luciferase reporter assays, rescue, and western blotting assays confirmed the interactions between circPGD, miR-16-5p, and ABL2. Transwell, wound healing, and colony-formation assays, as well as CCK-8 and cell apoptosis assays, analyzed the functions of circPGD, miR-16-5p, ABL2, as well as PGD-219aa within GC cells. Western blotting and cell immunofluorescence experiments detected the differences in the expression of the related proteins. Finally, xenograft and metastatic mouse models were used to investigate circPGD function in vivo. Mass spectrometry was used to detect the existence of PGD-219aa in MGC-803 cells. CircPGD was localized in the cytoplasm and nucleus of MGC-803 cells. Compared with the control, circPGD and ABL2 expression increased within GC tissues and cells, and the miR-16-5p level was decreased. Functionally, circPGD promoted cell proliferation, migration and suppressed apoptosis in vitro. Mechanistically, circPGD sponged miR-16-5p for relieving miR-16-5p suppression on the corresponding target ABL2 via the SMAD2/3 and YAP signaling pathways. In addition, circPGD encodes a novel PGD-219aa protein that can enhance the growth and migration of GC cells, while inhibiting GC cells apoptosis via the SMAD2/3 and YAP signaling pathways. Furthermore, circPGD overexpression enhanced tumor aggressiveness, while circPGD knockdown inhibited tumor growth. Overall, circPGD has a novel oncogenic effect on GC cells, indicating the potential of circPGD as the tumorigenic factor and a promising diagnostic marker for GC.
| S-EPMC9472197 | biostudies-literature
Project description:PurposeThis study aimed to explore the role of the long non-coding RNA (lncRNA) RNA component of mitochondrial RNAase P (RMRP) in sepsis-induced acute kidney injury (AKI).Materials and methodsVenous blood was collected from septic patients and healthy people. C57BL/6 mice who underwent cecal ligation and puncture (CLP) were used as in vivo models of septic AKI. Lipopolysaccharide (LPS)-induced HK-2 cells were employed as in vitro models of AKI. Flow cytometry analysis was conducted to detect cell apoptosis. Enzyme-linked immunosorbent assay and Western blot assays were used to detect levels of pro-inflammatory cytokines.ResultsRMRP was upregulated in sera from patients with AKI and in LPS-induced cells. Knockdown of RMRP inhibited cell apoptosis and reduced production of inflammatory factors in LPS-induced cells, as well as alleviated AKI in CLP mice. RMRP facilitated inflammation by activating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome. We found that microRNA 206 (miR-206) binds with and is negatively regulated by RMRP: miR-206 directly targets the 3' untranslated region of DEAD-box helicase 5 (DDX5) and negatively regulates DDX5 expression. By binding with miR-206, RMRP upregulated DDX5 expression. Rescue assays revealed that overexpression of DDX5 counteracted the effect of RMRP inhibition on cell apoptosis and inflammatory response in LPS-induced cells.ConclusionThe lncRNA RMRP contributes to sepsis-induced AKI through upregulation of DDX5 in a miR-206 dependent manner and through activation of NLRP3 inflammasome. This novel discovery may provide a potential strategy for treating AKI.
| S-EPMC7934096 | biostudies-literature
Project description:Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p-SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p-SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.
| S-EPMC8222372 | biostudies-literature
Project description:BackgroundBladder cancer (Bca) is the most common malignant tumor of the urinary system. Circular RNAs (circRNAs) have been recognized as key regulators in tumorigenesis. However, the molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown.MethodsWe detected the expression level of circular RNA TAF4B (circTAF4B) by qRT-PCR assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Wound healing and Transwell assays were performed to measure cell migration and invasion capability. Moreover, we performed qRT-PCR and western blotting assays to determine the expression levels of epithelial-mesenchymal transition (EMT) markers. A nuclear/cytoplasmic fractionation assay was used to measure the subcellular location of circTAF4B. RNA pull-down and dual-luciferase reporter assays were used to detect the target microRNA of circTAF4B. A mouse xenograft model was produced to analyze the effect of circTAF4B on the tumorigenesis of BCa.ResultsIn this study, we identified a novel circular RNA, circTAF4B, that is significantly upregulated in BCa and correlated with poor prognosis. Downregulated circTAF4B abolished the growth, metastasis and EMT process in BCa cells. Mechanistically, we found that circTAF4B facilitated the expression of transforming growth factor A (TGFA) by sponging miR-1298-5p. Finally, circTAF4B enhanced the proliferation and EMT process of BCa cells in vivo.ConclusionIn summary, our study demonstrated that circTAF4B played a carcinogenic role in the growth, metastasis, and EMT process of BCa by regulating the miR-1298-5p/TGFA axis. Thus, circTAF4B may become a diagnostic and therapeutic target for BCa.
| S-EPMC8312550 | biostudies-literature