Long noncoding RNA POU6F2-AS1 regulates lung cancer aggressiveness through sponging miR-34c-5p to modulate KCNJ4 expression.
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ABSTRACT:
SUBMITTER: Wu XY
PROVIDER: S-EPMC8127722 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lung adenocarcinoma (LUAD) is the most prevalent histological subclass of non-small cell lung cancer. Long non-coding RNAs (lncRNAs) have been recognized as the crucial regulatory factors in tumor development and progression. Nevertheless, limited research has been carried on the function of PRKCZ-AS1 in LUAD. In this study, the expression of PRKCZ-AS1 in LUAD tissues and cell lines was notably upregulated. Moreover, knockdown of PRKCZ-AS1 inhibited the proliferation and migration, but promoted apoptosis in LUAD cells. Furthermore, miR-766-5p could bind with PRKCZ-AS1. Besides, the expression miR-766-5p was negatively regulated by PRKCZ-AS1 expression in LUAD cells. Furtherly, PRKCZ-AS1 expression positively regulated the expression of MAPK1. Similarly, the expression of MAPK1 was negatively regulated by miR-766-5p expression. Moreover, the binding ability between miR-766-5p and MAPK1 was confirmed. Furthermore, knockdown of MAPK1 partly rescued the miR-766-5p inhibition-mediated promoting effect on proliferation and migration in LUAD cells transfected with PRKCZ-AS1#1. Overall, above results suggested that PRKCZ-AS1 promotes the occurrence of LUAD by sponging miR-766-5p to upregulate MAPK1 expression, which may provide new insights into LUAD treatment.
| S-EPMC7515500 | biostudies-literature
Project description:Dysregulation of non-coding RNAs (ncRNAs) has been proved to play pivotal roles in epithelial-mesenchymal transition (EMT) and fibrosis. We have previously demonstrated the crucial function of long non-coding RNA (lncRNA) ATB in silica-induced pulmonary fibrosis-related EMT progression. However, the underlying molecular mechanism has not been fully elucidated. Here, we verified miR-29b-2-5p and miR-34c-3p as two vital downstream targets of lncRNA-ATB. As opposed to lncRNA-ATB, a significant reduction of both miR-29b-2-5p and miR-34c-3p was observed in lung epithelial cells treated with TGF-β1 and a murine silicosis model. Overexpression miR-29b-2-5p or miR-34c-3p inhibited EMT process and abrogated the pro-fibrotic effects of lncRNA-ATB in vitro. Further, the ectopic expression of miR-29b-2-5p and miR-34c-3p with chemotherapy attenuated silica-induced pulmonary fibrosis in vivo. Mechanistically, TGF-β1-induced lncRNA-ATB accelerated EMT as a sponge of miR-29b-2-5p and miR-34c-3p and shared miRNA response elements with MEKK2 and NOTCH2, thus relieving these two molecules from miRNA-mediated translational repression. Interestingly, the co-transfection of miR-29b-2-5p and miR-34c-3p showed a synergistic suppression effect on EMT in vitro. Furthermore, the co-expression of these two miRNAs by using adeno-associated virus (AAV) better alleviated silica-induced fibrogenesis than single miRNA. Approaches aiming at lncRNA-ATB and its downstream effectors may represent new effective therapeutic strategies in pulmonary fibrosis.
| S-EPMC8335671 | biostudies-literature
Project description:BackgroundAs a newfound type of non-coding RNA, circular RNAs (circRNAs) are involved in various physiological and pathological processes via regulation of gene expression. Increasing evidence shows that aberrantly expressed circRNAs play a crucial role in the initiation and progression of many tumors. However, the functions of different circRNAs in gliomas remain elusive.MethodsThe levels of circRNAs, miRNAs, and mRNAs were quantified by qPCR. The interaction between circDENND2A and miR-625-5p was determined by luciferase reporter and pull-down assays. The migratory and invasive capabilities of glioma cells were examined by wound healing and Transwell assays. Immunohistochemistry was performed to analyze the HIF1α level in glioma tissues.ResultsWe predicted circDENND2A (has_circ_0002142) to be a hypoxia-responsive circRNA in glioma via a bioinformatic analysis. We found that hypoxia induced the expression of circDENND2A, which promoted migration and invasion of glioma cells. To understand the behaviors of circDENND2A in glioma, we studied the putative miRNAs targeted by circDENND2A and identified circDENND2A as an efficient sponge of miR-625-5p in glioma cells. Phenotype experiments verified that circDENND2A was required for the hypoxia-induced migration and invasion of glioma cells and that this occurred by sponging of miR-625-5p. Notably, glioma tissues overexpressing HIF1α exhibited a high expression of circDENND2A as well as a low expression of miR-625-5p. circDENND2A was negatively correlated with miR-625-5p.ConclusioncircDENND2A is required for the hypoxia-induced malignancy of glioma cells and functions by sponging miR-625-5p.
| S-EPMC6446274 | biostudies-literature
Project description:AimsLong non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.MethodsUsing quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.ResultsThe expression of PCBP1-AS1 was pre-eminent in OP tissues and decreased throughout the development of human bone marrow-derived mesenchymal stem cells (hBMSCs) into osteoblasts. PCBP1-AS1 knockdown and overexpression respectively promoted and suppressed hBMSC proliferation and osteogenic differentiation capacity. Mechanistically, PCBP1-AS1 sponged miR-126-5p and consequently targeted PAK2. Inhibiting miR-126-5p significantly counteracted the beneficial effects of PCBP1-AS1 or PAK2 knockdown on hBMSCs' ability to differentiate into osteoblasts.ConclusionPCBP1-AS1 is responsible for the development of OP and promotes its progression by inducing PAK2 expression via competitively binding to miR-126-5p. PCBP1-AS1 may therefore be a new therapeutic target for OP patients.
| S-EPMC10259264 | biostudies-literature
Project description:ObjectivesLung adenocarcinoma (LUAD) exhibits a higher fatality rate among all cancer types worldwide, yet the precise mechanisms underlying its initiation and progression remain unknown. Mounting evidence suggests that long non-coding RNAs (lncRNAs) exert significant regulatory roles in cancer development and progression. Nevertheless, the precise involvement of lncRNA CYP4A22-AS1 in LUAD remains incompletely comprehended.MethodsBioinformatics analyses evaluated the expression level of CYP4A22-AS1 in lung adenocarcinoma and paracancer. The LUAD cell line with a high expression of CYP4A22-AS1 was constructed to evaluate the role of CYP4A22-AS1 in the proliferation and metastasis of LUAD by CCK8, scratch healing, transwell assays, and animal experiments. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. Luciferase reporter gene analyses, west-blotting, and qRT-PCR were carried out to reveal the interaction between CYP4A22-AS1, miR-205-5p/EREG, and miR-34c-5p/BCL-2 axes.ResultsCYP4A22-AS1 expression was significantly higher in LUAD tissues than in the adjacent tissues. Furthermore, we constructed a LUAD cell line with a high expression of CYP4A22-AS1 and noted that the high expression of CYP4A22-AS1 significantly enhanced the proliferation and metastasis of LUAD. We applied transcriptome and microRNA sequencing to examine the mechanism of CYP4A22-AS1 enhancing the proliferation and metastasis of LUAD. CYP4A22-AS1 increased the expression of EREG and BCL-2 by reducing the expression of miR-205-5p and miR-34-5p and activating the downstream signaling pathway of EGFR and the anti-apoptotic signaling pathway of BCL-2, thereby triggering the proliferation and metastasis of LUAD. The transfection of miR-205-5p and miR-34-5p mimics inhibited the role of CYP4A22-AS1 in enhancing tumor progression.ConclusionThis study elucidates the molecular mechanism whereby CYP4A22-AS1 overexpression promotes LUAD progression through the miR-205-5p/EREG and miR-34c-5p/BCL-2 axes.
| S-EPMC10478502 | biostudies-literature
Project description:BackgroundColorectal cancer (CRC) is a malignant tumor affecting people worldwide. Long noncoding RNAs (lncRNAs) is a crucial factor modulating various cancer progression, including CRC. Long intergenic non-protein coding RNA 665 (LINC00665) has been proven as an oncogene in several cancers, but its function in CRC is still unclear.MethodsQRT-PCR was performed for RNA quantification. Functional assays were designed and carried to test cell phenotype while mechanism experiments were adopted for detecting the interaction of LINC00665, microRNA-138-5p (miR-138-5p) and SIN3 transcription regulator family member A (SIN3A). In vivo experiments were conducted to test LINC00665 function on modulating CRC tumor progression.ResultsLINC00665 displayed high expression in CRC tissues and cells, and promoted tumor progression in vivo. MiR-138-5p displayed abnormally low expression in CRC, and was verified to be sponged by LINC00665. Furthermore, SIN3A, as the downstream mRNA of miR-138-5p, exerted promoting impacts on CRC cells. Rescue experiments certified that overexpressed SIN3A or silenced miR-138-5p could offset the repressed function of LINC00665 knockdown on CRC progression.ConclusionsLINC00665 could sponge miR-138-5p to up-regulate SIN3A expression, thus accelerating CRC progression.
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Project description:In this study, we investigated the functional and clinical significance of the long non-coding RNA (lncRNA) FAM181A-AS1 in human gliomas. TCGA, GTEx and CGGA database analyses showed that high FAM181A-AS1 expression correlates with advanced tumor stage and poor survival of glioma patients. FAM181A-AS1 expression is higher in glioma cell lines compared to normal human astrocytes (NHA). CCK-8, EdU, and colony formation assays show that FAM181A-AS1 knockdown decreases proliferation and colony formation in glioma cells, whereas, FAM181A-AS1 overexpression reverses these effects. Bioinformatics analysis showed that miR-129-5p is a potential target of FAM181A-AS1. MiR-129-5p expression negatively correlates with FAM181A-AS1 expression in glioma patients. Dual luciferase reporter assays confirmed that miR-129-5p binds directly to FAM181A-AS1 in glioma cells. RNA immunoprecipitation (RIP) assays using anti-Ago2 antibody pulled down FAM181A-AS1 with miR-129-5p. Bioinformatics analysis identified ZRANB2 as a potential miR-129-5p target gene. Dual luciferase reporter assays confirmed that miR-129-5p binds directly to the 3'-UTR of ZRANB2 mRNA. Furthermore, miR-129-5p overexpression or ZRANB2 knockdown reduces proliferation and colony formation of FAM181A-AS1 overexpressing glioma cells. These findings show that FAM181A-AS1 promotes gliomagenesis by enhancing ZRANB2 expression by sponging of miR-129-5p.
| S-EPMC7655169 | biostudies-literature
Project description:Podocyte apoptosis exerts a crucial role in the pathogenesis of DN. Recently, long noncoding RNAs (lncRNAs) have been gradually identified to be functional in a variety of different mechanisms associated with podocyte apoptosis. This study aimed to investigate whether lncRNA Glis2 could regulate podocyte apoptosis in DN and uncover the underlying mechanism. The apoptosis rate was detected by flow cytometry. Mitochondrial membrane potential (ΔΨM) was measured using JC-1 staining. Mitochondrial morphology was detected by MitoTracker Deep Red staining. Then, the histopathological and ultrastructure changes of renal tissues in diabetic mice were observed using periodic acid-Schiff (PAS) staining and transmission electron microscopy. We found that lncRNA Glis2 was significantly downregulated in high-glucose cultured podocytes and renal tissues of db/db mice. LncRNA Glis2 overexpression was found to alleviate podocyte mitochondrial dysfunction and apoptosis. The direct interaction between lncRNA Glis2 and miR-328-5p was confirmed by dual luciferase reporter assay. Furthermore, lncRNA Glis2 overexpression alleviated podocyte apoptosis in diabetic mice. Taken together, this study demonstrated that lncRNA Glis2, acting as a competing endogenous RNA (ceRNA) of miRNA-328-5p, regulated Sirt1-mediated mitochondrial dysfunction and podocyte apoptosis in DN.
| S-EPMC10951868 | biostudies-literature
Project description:LncRNA FOXD2-AS1 is abnormally expressed in many diseases. However, the molecular mechanisms whereby FOXD2-AS1 is involved in recurrent pterygium remain unknown. Here, qRT-PCR was performed to quantify FOXD2-AS1 expression, while CCK-8, flow cytometer and neoplasm xenograft assays were used to investigate its function. Dual-luciferase reporter, RIP and RNA pull-down assays were conducted to address the relationship between FOXD2-AS1, miR-205-5p and VEGF-A, while ChIP assays were used to detect H3K27 acetylation at the FOXD2-AS1 promoter. FOXD2-AS1 expression was up-regulated in recurrent pterygium tissues. Moreover, a high FOXD2-AS1 expression was associated with advanced stages, increased microvessel density and shorter recurrent-free survival. In addition, ROC analysis showed that FOXD2-AS1 is a valid predictor of recurrent pterygium. Furthermore, we show that FOXD2-AS1 induced proliferation and inhibited apoptosis in a cell line derived from recurrent pterygia (HPF-R) at least partially through the regulation of the miR-205-VEGF pathway. In addition, the up-regulation of FOXD2-AS1 was attributed to the H3K27 acetylation at the promoter region. In conclusion, FOXD2-AS1 is activated via its H3K27 acetylation and regulates VEGF-A expression by sponging miR-205-5p in recurrent pterygium. Our results may provide a basis for the development of new therapeutic targets and biomarkers for recurrent pterygium.
| S-EPMC7754060 | biostudies-literature
Project description:Long non‑coding RNAs (lncRNAs) play a crucial role in cancer development. However, researchers have yet to identify the underlying association between lncRNAs and ovarian cancer (OC). The aim of the present study was to examine the effect of lncRNA RHPN1‑AS1 (RHPN1‑AS1) on OC cells and tissues. Reverse transcriptase‑quantitative PCR (RT‑qPCR) was utilized to quantify RHPN1‑AS1, miR‑485‑5p, and TPX2 mRNA expression in samples with OC. Luciferase‑reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull‑down assay were then employed to validate the target relationship among RHPN1‑AS1, miR‑485‑5p and TPX2. Cell Counting Kit‑8, BrdU, wound‑healing, cell‑adhesion, and flow cytometry assays were also employed to assess cell viability, proliferation, migration, adhesion and apoptosis, respectively, in SKOV3 and OVCAR3 cell lines. Findings revealed that RHPN1‑AS1 demonstrated a higher expression level in OC cell lines and tissues. In addition, RHPN1‑AS1 enhanced the adhesion, proliferation and migration of OC cell lines but decreased apoptosis of OC cells. It was also observed that the relationship between RHPN1‑AS1 and miR‑485‑5p was negative and that RHPN1‑AS1 could sponge miR‑485‑5p to regulate the proliferation, apoptosis, adhesion, and migration abilities of OC cells. Moreover, TPX2 was targeted by miR‑485‑5p and was significantly overexpressed in OC cell lines and tissues. Experimental investigations also revealed that TPX2 promoted the proliferation, adhesion, and migration of OC cells but suppressed the apoptosis of SKOV3 and OVCAR3 cells. In summary, RHPN1‑AS1 played a tumor promotive role by sponging miR‑485‑5p to increase TPX2 expression in OC tumorigenesis.
| S-EPMC8082340 | biostudies-literature