LncRNA FGD5‑AS1 promotes breast cancer progression by regulating the hsa‑miR‑195‑5p/NUAK2 axis.
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ABSTRACT:
SUBMITTER: Fang K
PROVIDER: S-EPMC8072314 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Long noncoding RNAs (lncRNAs) regulate cancer progression and drug resistance. However, the role of lncRNA FGD5-AS1 in regulating colon cancer (CC) progression is still largely unknown. Hence, this study investigated the role of lncRNA FGD5-AS1 in regulating colon cancer (CC) progression and found that lncRNA FGD5-AS1 regulated miR-497-5p/PD-L1 axis to promote cancer progression in CC cells in vitro and in vivo. Specifically, we found that lncRNA FGD5-AS1 and PD-L1 tended to be high-expressed, while miR-497-5p was low-expressed in CC tissues and cell lines compared to the normal adjacent tissues and cells. Next, we found that lncRNA FGD5-AS1 positively regulated PD-L1 in CC cells by sponging miR-497-5p. Finally, our gain- and loss-of-function experiments evidenced that the lncRNA FGD5-AS1/miR-497-5p/PD-L1 axis regulates CC progression. Functionally, the data suggested that lncRNA FGD5-AS1 positively regulated while miR-497-5p negatively modulated malignant phenotypes, including cell proliferation, viability, invasion, migration, epithelial-mesenchymal transition (EMT), and tumorigenesis in CC cells. Interestingly, the inhibiting effects of lncRNA FGD5-AS1 ablation on CC development were abrogated by both silencing miR-497-5p and upregulating PD-L1. This study found that lncRNA FGD5-AS1 sponged miR-497-5p to upregulate PD-L1, resulting in CC progression, and provided novel agents for CC diagnosis and prognosis.
| S-EPMC9279048 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) contribute to multiple biological processes in human glioblastoma (GBM). However, identifying a specific lncRNA target remains a challenge. In this study, bioinformatics methods and competing endogenous RNA (ceRNA) network regulatory rules were used to identify GBM-related lncRNAs and revealed that OXCT1 antisense RNA 1 (OXCT1-AS1) is a potential therapeutic target for the treatment of glioma.MethodsBased on the Gene Expression Omnibus (GEO) dataset, we identified differential lncRNAs, microRNAs and mRNAs and constructed an lncRNA-associated ceRNA network. The novel lncRNA OXCT1-AS1 was proposed to function as a ceRNA, and its potential target miRNAs were predicted through the database LncBase Predicted v.2. The expression patterns of OXCT1-AS1 in glioma and normal tissue samples were measured. The effect of OXCT1-AS1 on glioma cells was checked using the Cell Counting Kit 8 assay, cell colony formation assay, Transwell assay and flow cytometry in vitro. The dual-luciferase activity assay was performed to investigate the potential mechanism of the ceRNA network. Finally, orthotopic mouse models of glioma were created to evaluate the influence of OXCT1-AS1 on tumour growth in vivo.ResultsIn this study, it was found that the expression of lncRNA OXCT1-AS1 was upregulated in both The Cancer Genome Atlas (TCGA) GBM patients and GBM tissue samples, and high expression of OXCT1-AS1 predicted a poor prognosis. Suppressing OXCT1-AS1 expression significantly decreased GBM cell proliferation and inhibited cell migration and invasion. We further investigated the potential mechanism and found that OXCT1-AS1 may act as a ceRNA of miR-195 to enhance CDC25A expression and promote glioma cell progression. Finally, knocking down OXCT1-AS1 notably attenuated the severity of glioma in vivo.ConclusionOXCT1-AS1 inhibits glioma progression by regulating the miR-195-5p/CDC25A axis and is a specific tumour marker and a novel potential therapeutic target for glioma treatment.
| S-EPMC8028723 | biostudies-literature
Project description:In this study, we evaluated the function and regulation of the long non-coding RNA (lncRNA) FAM83H-AS1 in triple-negative breast cancer (TNBC). Our data show that the FAM83H-AS1 levels are increased in human TNBC cells and tissues. Proliferation, migration, and invasion of TNBC cells are decreased by FAM83H-AS1 suppression, but increased by FAM83H-AS1 overexpression. Bioinformatics analysis revealed that miR-136-5p is a potential target of FAM83H-AS1. MiR-136-5p expression is decreased in TNBC tissues, and its overexpression suppresses TNBC cell proliferation, migration, and invasion. MiR-136-5p suppression reverses the FAM83H-AS1 silencing-mediated inhibition of TNBC cell proliferation, migration, and invasion, suggesting that FAM83H-AS1 exerts its oncogenic effect by inhibiting miR-136-5p. Our data identify metadherin (MTDH) as the target gene of miR-136-5p, and demonstrate that the MTDH expression is increased in human TNBC tissues, which induces proliferation, migration, and invasion of TNBC cells. Importantly, our in vivo data show that FAM83H-AS1 also promotes tumor growth in TNBC mouse xenografts. Together, our results demonstrate that FAM83H-AS1 functions as an oncogenic lncRNA that regulates miR-136-5p and MTDH expression during TNBC progression, and suggest that targeting the FAM83H-AS1/miR-136-5p/MTDH axis may serve as a novel therapeutic target in TNBC.
| S-EPMC7066879 | 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:BackgroundLong non-coding RNA FGD5 antisense RNA 1 (FGD5-AS1), identified to be a carcinogenic lncRNA, exhibits a regulatory role in some malignancies including non-small cell lung cancer (NSCLC). The aim of the present research is to decipher the function and underlying mechanism of FGD5-AS1 in progression of NSCLC.MethodsExpression of FGD5-AS1, miR-493-5p and DEAD-box protein 5 (DDX5) in NSCLC tissues and cells was quantified utilizing qRT-PCR. Cell proliferation was assessed by CCK-8 method. Scratch healing test and Transwell assay were used for assaying cell migration and invasion. Expressions of DDX5 and epithelial-mesenchymal transition (EMT)-related proteins were examined by Western blot. Additionally, targeting relationships between FGD5-AS1 and miR-493-5p, miR-493-5p and DDX5 were verified by dual-luciferase reporter gene assay.ResultsExpression of FGD5-AS1 in NSCLC tissues and cell lines was up-regulated. Expression of FGD5-AS1 was in association with enlarged tumor size and lymph node metastasis of the patients. Knockdown of FGD5-AS1 led to the inhibition of proliferation, migration, invasion and EMT of NSCLC cells. FGD5-AS1 directly targeted miR-493-5p, while DDX5 was the target of miR-493-5p in NSCLC cells. Additionally, FGD5-AS1 could positively regulate the expression of DDX5 via suppressing miR-493-5p.ConclusionFGD5-AS1 facilitates the proliferation, migration, invasion and EMT of NSCLC cells by sponging miR-493-5p and up-regulating DDX5.
| S-EPMC7876571 | biostudies-literature
Project description:ObjectiveOsteoarthritis (OA) is a common joint disorder, accompanied by extracellular matrix (ECM) degradation. Reportedly, long noncoding RNAs (lncRNAs) are involved in OA pathogenesis. However, the role of lncRNA FYVE, RhoGEF, and PH domain containing 5 antisense RNA 1 (FGD5-AS1) in OA development is still not fully clarified. This study was aimed to clarify the role of FGD5-AS1 in OA.MethodsFGD5-AS1 and miR-302d-3p expression levels were determined in cartilage tissues and chondrocytes by quantitative real-time polymerase chain reaction (qRT-PCR). Chondrocytes (C20/A4 cells) were stimulated with interleukin 1β (IL-1β) to mimic the inflammatory environment of OA. Cell viability was detected by cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Cell apoptosis was measured by the caspase-3 activity assay and flow cytometry. Transforming growth factor beta receptors II (TGFBR2), matrix metalloproteinase 13 (MMP-13), and ADAM metallopeptidase with thrombospondin type 1 motif 5 expression levels were examined by qRT-PCR or Western blot. The regulatory relationships among FGD5-AS1, miR-302d-3p, and TGFBR2 were predicted by the StarBase v2.0, miRanda, miRDB, and TargetScan databases, and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay.ResultsFGD5-AS1 and TGFBR2 expression levels were downregulated while miR-302d-3p expression was increased in cartilage tissues of OA patients. Knocking down FGD5-AS1 inhibited the viability of C20/A4 cells but induced apoptosis and ECM degradation, while FGD5-AS1 overexpression exerted opposite effects. MiR-302d-3p was identified as a target of FGD5-AS1, and TGFBR2 was identified as a target of miR-302d-3p. FGD5-AS1 positively regulated TGFBR2 expression by repressing miR-302d-3p expression, and miR-302d-3p inhibition or TGFBR2 restoration reversed the changes of cell viability, apoptosis, and ECM degradation induced by FGD5-AS1 knockdown.ConclusionFGD5-AS1 can probably inhibit OA progression by regulating miR-302d-3p/TGFBR2 axis.
| S-EPMC8804797 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are related to the initiation and progression of tumor and regulate various cellular processes including growth, invasion, migration, and apoptosis. Understanding the roles and mechanisms of lncRNAs in regulating cancer progression is crucial for formulating novel therapeutic strategies. Although lncRNA DCST1-antisense RNA 1(AS1) has been implicated in several cancers, its role in the progression of colorectal cancer (CRC) remains to be explored. This study focuses on elucidating the function of lncRNA DCST1-AS1 in CRC development and its underlying mechanism. We found that the expression of lncRNA DCST1-AS1 was up-regulated in CRC tissues and cell lines, and CRC patients with high lncRNA DCST1-AS1 expression were associated with a poor prognosis. Loss-of-function and gain-of-function experiment in CRC cell lines confirmed that lncRNA DCST1-AS1 promoted the malignant phenotype of CRC cells, including cell proliferation, colony formation, migration, and invasion. In addition, we identified the binding sites between lncRNA DCST1-AS1 and hsa-miR-582-5p, and between hsa-miR-582-5p and High Mobility Group Box 1 (HMGB1) through DIANA Tools and TargetScan database, which was further confirmed by dual-luciferase reporter assay. Functional assay further confirmed the crucial role of lncRNA DCST1-AS1/hsa-miR-582-5p/HMGB1 axis in modulating the malignant phenotype of CRC cells. Collectively, our data suggest that lncRNA DCST1-AS1 regulates the aggressiveness of CRC cells through hsa-miR-582-5p/HMGB1 axis. Our study provides novel insight into the mechanism of lncRNA DCST1-AS1 in CRC cells for targeted therapy.
| S-EPMC8805871 | biostudies-literature
Project description:Long non-coding RNA (lncRNA) is essential to the development and progression of malignant human cancer. Growing evidence suggests that the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) is a crucial regulatory effector for multiple cancer types and is closely associated with poor prognosis. However, in most cases, the molecular mechanism underlying the role of FOXD3-AS1 in cancer development has not yet been fully elucidated. The present study focused on non-small cell lung cancer (NSCLC) in order to gain insight into how FOXD3-AS1 drives cancer progression. First, FOXD3-AS1 expression in NSCLC tissue samples was detected using reverse transcription-quantitative (RT-qPCR). Moreover, cell proliferation and apoptosis were determined using Cell Counting Kit-8 assays and flow cytometry, respectively. A luciferase reporter assay was then performed to determine whether there was a direct binding association between FOXD3-AS1 and microRNA (miR)-135a-5p. Lastly, a tumor subcutaneous xenograft model was established to examine the role of FOXD3-AS1 in tumor growth. FOXD3-AS1 was significantly overexpressed in NSCLC tissue samples and cell lines compared with normal tissue samples and cells. FOXD3-AS1 silencing expression significantly inhibited A549 and H1229 cell proliferation while inducing apoptosis compared with sh-NC group. The luciferase reporter assay demonstrated the direct binding interaction between FOXD3-AS1 and miR-135a-5p. Moreover, FOXD3-AS1 silencing led to the upregulation of miR-135a-5p in A549 and H1229 cells compared with sh-NC group. It was also demonstrated that miR-135a-5p could bind to the 3' untranslated region of cyclin-dependent kinase 6 (CDK6) and negatively modulate its transcription. miR-135a-5p knockdown or CDK6 overexpression reversed the inhibition on cell proliferation and apoptosis following FOXD3-AS1 knockdown. Altogether, the present study suggests that FOXD3-AS1 sponges miR-135a-5p to promote cell proliferation and concomitantly inhibit apoptosis by regulating CDK6 expression in NSCLC cells.
| S-EPMC8561623 | biostudies-literature
Project description:BackgroundThe abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear.MethodsTo explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied.ResultsOIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells.ConclusionsOIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment.
| S-EPMC9486127 | biostudies-literature
Project description:BackgroundBreast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear.MethodsWe conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis.ResultsTDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC.ConclusionsOur study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.
| S-EPMC10676586 | biostudies-literature