Opa-interacting Protein 5 Antisense RNA 1 Research Articles

GATA1-activated lncRNA OIP5-AS1 and GAS5 promote pyroptosis to exacerbate asthma through regulating miR-136-5p/LIFR axis.

Pyroptosis plays a pivotal role in airway epithelial inflammation during the progression of asthma. This study aimed to explore the influence and mechanisms of opa-interacting protein 5 antisense RNA1 (OIP5-AS1) and growth arrest-specific transcript 5 (GAS5) on pyroptosis in asthmatic models. Pyroptosis was induced in Dermatophagoides pteronyssinus 1 (Der p1)-exposed 16HBE cells and ovalbumin (OVA)-challenged rats. Subsequently, pyroptosis and its related molecular mechanisms were investigated. Our results indicated that GATA1, OIP5-AS1, GAS5, and LIFR were upregulated, while miR-136-5p was downregulated in the patients and experimental models of asthma. OIP5-AS1/GAS5 knockdown repressed NLRP3 inflammasome-mediated pyroptosis in 16HBE cells. Mechanistically, OIP5-AS1/GAS5 sponged miR-136-5p to enhance LIFR expression and subsequently activated NF-κB pathway. OIP5-AS1, GAS5, or LIFR-mediated induction of pyroptosis was abrogated by miR-136-5p mimics or NF-κB inhibitors (BAY11-7082). Finally, GATA1 transcriptionally activated OIP5-AS1/GAS5 to trigger pyroptosis, thereby driving asthma progression invivo and invitro. In conclusion, OIP5-AS1/GAS5 transcriptionally activated by GATA1 promoted NLRP3 inflammasome-mediated pyroptosis via the modulation of miR-136-5p/LIFR/NF-κB axis and consequently resulted in airway inflammation in asthma. Our results may provide novel therapeutic strategies for asthma.

In-Silico and In-Vitro Investigation of Key Long Non-coding RNAs Involved in 5-Fluorouracil Resistance in Colorectal Cancer Cells: Analyses Highlighting NEAT1 and MALAT1 as Contributors.

Background Acquired resistance to 5-fluorouracil (5-FU) frequently results in chemotherapy failure and disease recurrence in advanced colorectal cancer (CRC) patients. Research has demonstrated that dysregulation of long non-coding RNAs (lncRNAs) mediates the development of chemotherapy resistance in cancerous cells. The present study aims to identify key lncRNAs associated with 5-FU resistance in CRC using bioinformatic and experimental validation approaches. Methods The Gene Expression Omnibus (GEO) dataset GSE119481, which contains miRNA expression profiles of the parental CRC HCT116 cell line (HCT116/P) and its in-vitro established 5-FU-resistant sub-cell line (HCT116/FUR), was downloaded. Firstly, differentially expressed microRNAs (DEmiRNAs) between the parental and 5-FU resistance cells were identified. LncRNAs and mRNAs were then predicted using online databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to uncover relevant biological mechanisms and pathways. Networks integrating lncRNAs, miRNAs, and mRNAs interactions were constructed, and topological analyses were used to identify key lncRNAs associated with 5-FU resistance. An in-vitro model of the HCT116/FUR sub-cell line was developed by exposing the HCT116/P cell line to increasing concentrations of 5-FU. Finally, real-time quantitative PCR (RT-qPCR) was performed on total RNA extracted from the HCT116/P cell line and the HCT116/FUR sub-cell line to validate the in-silico predictions of key lncRNAs. Results A total of 32 DEmiRNAs were identified. Enrichment analysis demonstrated that these DEmiRNAs were mainly enriched in several cancer hallmark pathways that regulate cell growth, cell cycle, cell survival, inflammation, immune response, and apoptosis. The predictive analysis identified 237 unique lncRNAs and 123 mRNAs interacting with these DEmiRNAs. The pathway analysis indicated that most of these predicted genes were enriched in the cellular response to starvation, protein polyubiquitination, chromatin remodeling, and negative regulation of gene expression. Topological analyses of the lncRNA-miRNA-mRNA network highlighted the nuclear enriched abundant transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and Opa interacting protein 5 antisense RNA 1 (OIP5-AS1) as central lncRNAs. Experimental analysis by RT-qPCR confirmed that the expression levels of NEAT1 and MALAT1 were significantly increased in HCT116/FUR cells compared to HCT116/P cells. However, no significant difference was observed in the OIP5-AS1 expression level between the two cells. Conclusion Our findings specifically highlight MALAT1 and NEAT1 as significant contributors to 5-FU resistance in CRC. These lncRNAs are promising biomarkers for diagnosing and predicting outcomes in CRC.

OIP5-AS1/miR-455-3p/microfibril-associated protein 2 axis exacerbates the progression of thyroid carcinoma.

The long non-coding RNA (lncRNA) Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) has been shown to participate in numerous biological and pathological processes, notably including oncogenesis. OIP5-AS1 modulates oncogenic or anti-tumor activities by controlling various microRNAs (miRs) in diverse cancer types. This study sought to examine the potential role of the lncRNA OIP5-AS1-mediated miR-455-3p/microfibril-associated protein 2 (MFAP2) axis and its influence on the progression of thyroid carcinoma. Cell proliferation, migration, and apoptosis were assessed through in vitro experimental measurements, which involved the use of Cell Counting Kit 8 (CCK8), transwell, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining techniques. The estimate algorithm was employed to examine the relationship between MFAP2 and the Stromal score, Immune score, and ESTIMATE score. OIP5-AS1 expression was significantly more elevated in the thyroid carcinoma tissues and cell lines than the corresponding normal non-tumor tissues and cell lines. Following transfection with short-hairpin (sh)-OIP5-AS1, the CAL62 and SW1736 cells upregulated miR-455-3p and downregulated the MFAP2 expression levels. The downregulation of OIP5-AS1 expedited cellular apoptosis and hindered cellular proliferation and migration in the CAL62 and SW1736 cells. The in vitro experiments showed that both the suppression of MFAP2 and the increased expression of miR-455-3p exerted significant anti-cancer effects. In addition, the overexpression of MFAP2 counteracted the in vitro antineoplastic effects of the sh-OIP5-AS1 and miR-455-3p mimics. The results suggest that lncRNA OIP5-AS1 plays a crucial role in the advancement of thyroid carcinoma by inhibiting miR-455-3p to activate MFAP2.

LncRNA OIP5-AS1 promotes the proliferation and migration of vascular smooth muscle cells via regulating miR-141-3p/HMGB1 pathway

BackgroundLong non-coding RNAs (lncRNAs) have been reported to play critical roles in the pathogenesis of cardiovascular diseases. However, whether lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) regulates the pathogenesis of atherosclerosis (AS) is still unknown. MethodsHuman vascular smooth muscle cells (VSMCs) were treated with oxidized low-density lipoprotein (ox-LDL). OIP5-AS1, miR-141-3p and HMGB1 mRNA expressions were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and apoptosis of VSMCs were measured using MTT method, Transwell assay and TUNEL assay, respectively. Dual-luciferase reporter gene assay, qRT-PCR, and Western blot were conducted to investigate the interactions among OIP5-AS1, miR-141-3p and high mobility group box 1 (HMGB1). ResultsOIP5-AS1 expression was markedly increased in serum samples of AS patients and VSMCs treated with ox-LDL. OIP5-AS1 over-expression remarkably promoted proliferation, migration and inhibited apoptosis of VSMCs while miR-141-3p exerted the opposite effects. Furthermore, the binding sites between OIP5-AS1 and miR-141-3p were identified. OIP5-AS1 indirectly increased HMGB1 expression in VSMCs by targeting miR-141-3p. ConclusionsOIP5-AS1 promotes the proliferation, migration and suppresses apoptosis of VSMCs through regulating miR-141-3p/HMGB1 axis.

LncRNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) promotes the migration, invasion and epithelial-mesenchymal transition (EMT) through targeting miR-147a/insulin-like growth factor 1 receptor (IGF1R) pathway in cervical cancer tissues and cell model.

Two factors involved in regulation, long noncoding RNA Opa interacting protein 5-antisense RNA 1 (lncRNA OIP5-AS1) and microRNA-147a, were found in cervical cancer. Therefore, the investigation of the specific regulation of miR-147a by OIP5-AS1 was performed in cervical cancer. The cervical cancer tissues were collected from patients with cervical cancer (n=50). The expression of OIP5-AS1, miR-147a, proteins in epithelial-mesenchymal transition (EMT) process and insulin-like growth factor 1 receptor (IGF1R) were measured by quantitative real-time polymerase chain reaction (qRT-PCT) or western blotting. Cell motility and the relationship between OIP5-AS1 and miR-147a were detected or analyzed by wound healing test, Transwell assay, dual-luciferase reporter assay, RNA binding protein immunoprecipitation assay or Pearson correlation in OIP5-AS1, or miR-147a over-expressed and/or suppressed cervical cancer cells. OIP5-AS1 showed the high-expression and miR-147a showed the low-expression in tumor tissues collected from patients with cervical cancer and cell lines Hela, CaSki, Siha, and ME-180. The low-expression of OIP5-AS1 suppressed the motility of Caski cells, as well as up-regulated the level of E-cadherin, which a key protein in EMT. There were targeting sites between miR-147a and OIP5-AS1. OIP5-AS1 induced the down-regulation of miR-147a, so miR-147a was inversely correlated with OIP5-AS1. The down-regulation of miR-147a increased IGF1R and E-cadherin, and these increases were alleviated by OIP5-AS1 knockdown. LncRNA OIP5-AS1 promotes the migration, invasion and EMT of cervical cancer cells via targeting miR-147a/IGF1R pathway.

LncRNA OIP5-AS1 knockdown or miR-223 overexpression can alleviate LPS-induced ALI/ARDS by interfering with miR-223/NLRP3-mediated pyroptosis.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases and endothelial barrier injury is an important contributor to the pathogenesis of ALI/ARDS. Long non-coding (lncRNA) has been shown to participate in the progression of ALI/ARDS. The present study aimed to investigate the function of lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in lipopolysaccharide (LPS)-induced ALI/ARDS. OIP5-AS1 and miR-223 levels were detected by a polymerase chain reaction in the serum of ALI/ARDS patients or healthy donors. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was performed to detect the proliferation of human pulmonary microvascular endothelial cells (HPMECs). Flow cytometry were performed to detect the apoptosis of HPMECs. The protein levels of NLRP3, ASC, GSDMD-N and caspase-1 were measured by western blotting to detect the pyroptosis of HPMECs. Interleukin (IL)-1β, IL-6, IL-18 and IL-10 were detected by an enzyme-linked immunosorbent assay to measure the inflammatory response of HPMECs. The production of reactive oxygen species, superoxide dismutase and malondialdehyde was measured to determine the oxidative stress of HPMECs. Targets of OIP5-AS1 and miR-223 were predicted by StarBase and confirmed by a dual-luciferase reporter assay. We found that OIP5-AS1 was up-regulated and miR-223 was down-regulated in the serum of ALI/ARDS patients and LPS-treated HPMECs. Functionally, knockdown of OIP5-AS1 induced proliferation and inhibited apoptosis, pyroptosis, inflammatory response and oxidative stress of LPS-treated HPMECs. Interestingly, miR-223 was a target of OIP5-AS1 and miR-223 inhibition abolished the effects of si-OIP5-AS1 on LPS-induced HPMECs. More importantly, miR-223 directly targeted NLRP3, and miR-223 overexpression promoted proliferation and inhibited apoptosis, pyroptosis, inflammatory response and oxidative stress of LPS-treated HPMECs, with this being abolished by NLRP3 overexpression. Finally, we found that OIP5-AS1 knockdown and miR-223 overexpression could both alleviate LPS-induced ALI/ARDS in vivo. Taken together, we find that lncRNA OIP5-AS1 aggravates LPS-induced ALI/ARDS via miR-223/NLRP3 axis and provides new targets for ALI/ARDS therapy.

Cancer-associated fibroblasts-derived exosomes promote lung cancer progression by OIP5-AS1/ miR-142-5p/ PD-L1 axis

Cancer-associated fibroblasts (CAFs) are the most important stromal cells in the tumor microenvironment (TEM) and have been reported to regulate various cancer development. Exosomes are considered important elements involved in intercellular communication and TME regulation, while the potential function of CAFs in lung cancer immunosuppressive microenvironments remains unknown. CAFs-derived exosomes (CAFs-exo) and normal fibroblasts (NFs)-derived exosomes (NFs-exo) were isolated by ultra-centrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blot analysis. A549 cells were co-cultured with peripheral blood mononuclear cells (PBMCs). Flow cytometry assay was performed to detect the killing role of PBMCs on A549 cells. Bioinformatics and luciferase reporter assays were used to analyze the relationship among microRNA (miRNA), long non-coding RNA (lncRNA) and target gene. BALB/c mice were used to construct the lung cancer model by subcutaneous injection. Programmed death ligand 1 (PD-L1) was up-regulated in lung cancer tissues and cells. PD-L1 also up-regulated in CAFs cell medium-mediated A549 cells. CAFs decreased PBMCs induced-cell apoptosis through increasing PD-L1 in A549 cells. Moreover, CAFs transferred exosomes to lung cancer cells to suppress the killing effect of PBMCs through up-regulating PD-L1. Using microarray assays, opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) level was highly expressed in CAFs-exos. After treatment by CAFs-exos, miR-142-5p level was significantly down-regulated in A549 cells. OIP5-AS1 served as a sponge to target miR-142-5p and negatively regulated miR-142-5p expression in lung cancer cells. In addition, PD-L1 was a direct target of miR-142-5p. CAFs derived exosomal OIP5-AS1 reduced PBMCs induced-cell apoptosis and promoted tumor growth through decreasing miR-142-5p and up-regulating PD-L1. CAFs-derived exosomes suppressed the role of PBMCs induced-killing of lung cancer cells and promoted lung cancer progression by OIP5-AS1/ miR-142-5p/ PD-L1 axis, which provided a potential opportunity for diagnosis and treatment of lung cancer.

LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis

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.

Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

BackgroundAcute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI.MethodsWe used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI.ResultTLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis.ConclusionOIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

LncRNA OIP5-AS1 accelerates ox-LDL-treated HUVECs injury by NF-κB pathway via miR-30c-5p.

Oxidized low-density lipoprotein (ox-LDL) could induce endothelial injury and played a vital role in the progression and development of atherosclerosis. This study aimed to investigate the role of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in ox-LDL-induced human umbilical vascular endothelial cells (HUVECs) injury and the potential mechanisms. Cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay, respectively. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were detected by corresponding detection kits, respectively. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of OIP5-AS1 or microRNA-30c-5p (miR-30c-5p) in HUVECs. Binding between OIP5-AS1 and miR-30c-5p was predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze p-IκB, IκB, p-p65 and p65 levels. In HUVECs, exposure to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as evidenced by increased ROS and MDA generation, as well as decreased SOD activity and NO levels, while OIP5-AS1 knockdown or miR-30c-5p upregulation could rescue these effects above. Mechanically, OIP5-AS1 functioned as a sponge of miR-30c-5p. OIP5-AS1-induced injury and apoptosis, oxidative stress and activation of NF-κB pathway were reversed by miR-30c-5p in ox-LDL-treated HUVECs. OIP5-AS1 contributed to ox-LDL-treated HUVECs injury by activation of NF-κB pathway via miR-30c-5p.

Long noncoding RNA OIP5-AS1 exhibits oncogenic activity in bladder cancer through miR-217 and MTDH.

The aim of this study was to investigate the role of long non-coding Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in bladder cancer (BCa), and the mechanism of OIP5-AS1/microRNA-217 (miR-217)/metadherin (MTDH) in promoting the progression of BCa. OIP5-AS1, miR-217 and MTDH expressions in BCa tissues and cells were detected by qRT-PCR or Western blot. CCK-8 and transwell assays were used to determine the proliferation and invasion of BCa cells. The correlation between OIP5-AS1 and miR-217, miR-217 and MTDH, and OIP5-AS1 and MTDH were studied by Luciferase reporter assay and Spearman correlation analysis. Statistical analysis of test data was performed using t-test. OIP5-AS1 was upregulated in BCa tissues and cells, and OIP5-AS1 knockdown could inhibit the proliferation and invasion of BCa cells. MiR-217 was a direct-acting target of OIP5-AS1, and MTDH was a target of miR-217. OIP5-AS1 knockdown inhibits human BCa cell proliferation and invasion through miR-217/MTDH axis. This study systematically explored the effect of OIP5-AS1 in human BCa. MiR-217/MTDH pathway mediated the promotion of OIP5-AS1 in BCa cells proliferation and invasion. OIP5-AS1, as an oncogene, could be used as a biomarker for the treatment of BCa.

OPA Interacting Protein 5 Antisense RNA 1 Expedites Cell Migration and Invasion Through FOXM1/ Wnt/β-Catenin Pathway in Pancreatic Cancer.

Pancreatic cancer (PC) is a digestive tract malignancy with poor prognosis. Long noncoding RNA (lncRNA) OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was regarded to be correlated with human malignancy, working as tumor suppressor or promoter on the basis of tumor types. However, the function of OIP5-AS1 in PC remained unclear. The study focused on the function and regulatory mechanism of OIP5-AS1 in PC. OIP5-AS1 expression was assessed by the quantitative reverse transcription PCR (RT-qPCR) in tumor tissues and PC cell lines. 5-ethynyl-2'-deoxyuridine (EdU) incorporation and cell counting kit-8 (CCK-8) assays were applied to detect cell proliferation ability. Through wound healing and transwell assays, cell migration and invasion capacities were estimated. Flow cytometry analysis was performed to examine apoptosis capability of PC cells. OIP5-AS1 downregulating inhibited cell proliferation, migration, and invasion capacities, while promoting cell apoptosis rates. As a competing endogenous RNA (ceRNA), OIP5-AS1 competed with Forkhead Box M1 (FOXM1) for the binding sites on microRNA-320b (miR-320b). OIP5-AS1 was able to upregulate FOXM1 expression via silencing miR-320b. Furthermore, FOXM1 served as an activator of Wnt/β-catenin pathway and mediated the effect of OIP5-AS1 on Wnt/β-catenin pathway. OIP5-AS1 expedites the proliferative, migrated, and invasive capability of PC cells, while repressing cell apoptosis through regulating miRNA-320b/FOXM1 axis and FOXM1/Wnt/β-catenin pathway in PC. OIP5-AS1 regulation on FOXM1/Wnt/β-catenin pathway may offer novel efficient markers for PC treatments.

Long non-coding RNA OIP5-AS1 contributes to cisplatin resistance of oral squamous cell carcinoma through the miR-27b-3p/TRIM14 axis.

Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cavity cancer types, but the overall prognosis for patients with OSCC remains unfavorable. Cisplatin (DDP) is an effective drug in OSCC treatment, but DDP resistance weakens its therapeutic effect. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) can trigger DDP resistance. The purpose of the current study was to explore the role and mechanism ofOIP5-AS1 in OSCC DDP resistance. In the present study, the expression levels of OIP5-AS1, microRNA (miR)-27b-3p and tripartite motif-containing 14 (TRIM14) were detected by reverse transcription-quantitative PCR. DDP resistance was measured using an MTT assay. Moreover, cell proliferation, migration and invasion were assessed by MTT, Transwell, and Matrigel assays. Protein expression levels of TRIM14, E-cadherin, N-cadherin and Vimentin were detected by western blot analysis. Putative binding sites between miR-27b-3p andOIP5-AS1 or TRIM14werepredicted with starBase and verified using a dual-luciferase reporter assay. The role of OIP5-AS1 in DDP resistance of OSCC in vivo was measured using a xenograft tumor model. It was observed that OIP5-AS1 was upregulated in DDP-resistant OSCC cells, and the knockdown of OIP5-AS1 improved DDP sensitivity in DDP-resistant OSCC cells. The present study identified that miR-27b-3p was a target of OIP5-AS1. Furthermore, miR-27b-3p silencing reversed the effect of OIP5-AS1 knockdown on DDP sensitivity in DDP-resistant OSCC cells. TRIM14was shown to be a direct target of miR-27b-3p, and TRIM14 overexpression abolished the effect of miR-27b-3p on DDP sensitivity in DDP-resistant OSCC cells. The results suggested that OIP5-AS1 increased TRIM14 expression by sponging miR-27b-3p. In addition, OIP5-AS1 knockdown enhanced DDP sensitivity of OSCC in vivo. Data from the present study indicated that OIP5-AS1 may improve DDP resistance through theupregulationTRIM14 mediated bymiR-27b-3p, providing a possible therapeutic strategy for OSCC treatment.

Long Noncoding RNA OIP5-AS1 Promotes the Disease Progression in Nasopharyngeal Carcinoma by Targeting miR-203.

Nasopharyngeal carcinoma (NPC) is a kind of malignancy generated from the nasopharyngeal epithelium. Recently, long noncoding RNA (lncRNA) has been shown to be involved in the regulation of many signaling pathways and is closely associated with carcinogenesis and tumor progression. However, the precise role of lncRNA Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in NPC is not well understood. Here, we find that OIP5-AS1 is overexpressed in NPC patient specimens and NPC cell lines. Further investigations reveal that knockdown of OIP5-AS1 significantly inhibits the proliferation, migration, and invasion and accelerates the apoptosis of NPC cells in vitro. Consistent with these findings, NPC progression is significantly slowed in mice when OIP5-AS1 is knocked down. Interestingly, there is a functional link between OIP5-AS1 and microRNA-203 (miR-203), a tumor suppressor, in NPC cells. In conclusion, our data demonstrate that OIP5-AS1 plays an important role in the development and progression of NPC by targeting miR-203 and therefore provide a promising target for the treatment of NPC.

Up-regulating lncRNA OIP5-AS1 protects neuron injury against cerebral hypoxia-ischemia induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p

BackgroundInflammation and oxidative stress is closely associated with the development of ischemic brain stroke. Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a novel identified long non-coding RNA (lncRNA), has been suggested to play an important role in the development of many types of human cancers. However, the functional involvement of OIP5-AS1 in ischemic stroke is still unknown. MethodsQuantitative real-time polymerase chain reaction and /or western blot were conducted to determine the expression profiles of OIP5-AS1, C1q/TNF-related protein 3 (CTRP3) and miR-186-5p in the serum of stroke patients, as well as in the ischemic penumbra of rats with middle cerebral artery occlusion/reperfusion (MCAO/R) injury and microglial cells treated with oxygen glucose deprivation/re-oxygenation (OGD/R). Upon selective regulation of OIP5-AS1 and miR-186-5p, the inflammation and oxidative stress responses in microglia/macrophage as well as neurologic functions in MCAO/R rats were detected. Furthermore, the interactions between OIP5-AS1 and miR-186-5p, miR-186-5p and CTRP3 were investigated by RNA immunoprecipitation (RIP) assay, luciferase report assay and bioinformation anaylsis. ResultsWe observed markedly increased infarct volume, neuronal apoptosis, inflammation and oxidative stress responses in the infarcted lesions of MCAO/R rats, in line with down-regulated levels of OIP5-AS1 and CTRP3 while up-regulated miR-186-5p. Functional studies demonstrated that up-regulation of OIP5-AS1 attenuated infarct volume, neuronal apoptosis, microglia/macrophage inflammation and oxidative stress responses induced by MCAO/R or OGD/R. In terms of mechanism, we revealed that OIP5-AS1-miR-186-5p-CTRP3 axis played a vital role in modulating microglia/macrophage activation and neuronal apoptosis. ConclusionUp-regulating lncRNA OIP5-AS1 protects neuron injury against MCAO/R induced inflammation and oxidative stress in microglia/macrophage through activating CTRP3 via sponging miR-186-5p.

LncRNA OIP5-AS1 facilitates ox-LDL-induced endothelial cell injury through the miR-98-5p/HMGB1 axis.

Cerebrovascular diseases have a high mortality and disability rate in developed countries. Endothelial cell injury is the main cause of atherosclerosis and cerebrovascular disease. Long non-coding RNA (lncRNA) has been proved to participate in the progression of endothelial cell. Our study aimed to develop the function of lncRNA opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in oxidative low-density lipoprotein (ox-LDL)-induced endothelial cell injury. The expression of OIP5-AS1, miR-98-5p and High-mobility group protein box-1 (HMGB1) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect the cell proliferation and apoptosis. The levels of cyclinD1, Bcl-2 Associated X Protein (Bax), Cleaved-caspase-3, Toll like receptors 4 (TLR4), phosphorylation of p65 (p-P65), phosphorylation of nuclear factor-kappa B inhibitor α (p-IκB-α) and HMGB1 were measured by Western blot. The concentrations of Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The production of Reactive oxygen species (ROS), Superoxide Dismutase (SOD) and malondialdehyde (MDA) was detected by the corresponding kit. The targets of OIP5-AS and miR-98-5p were predicted by starBase 3.0 and TargetScan and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The expression of OIP5-AS1 was upregulated, while miR-98-5p was downregulated in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Functionally, knockdown of OIP5-AS1 induced proliferation and inhibited apoptosis, inflammatory injury and oxidative stress injury in ox-LDL-induced HUVEC cells. Interestingly, miR-98-5p was a target of OIP5-AS1 and miR-98-5p inhibition abolished the effects of OIP5-AS1 downregulation on ox-LDL-induced HUVECs injury. More importantly, miR-98-5p directly targeted HMGB1, and OIP5-AS1 regulated the expression of HMGB1 by sponging miR-98-5p. Finally, OIP5-AS1 regulated the TLR4/nuclear factor-kappa B (NF-κB) signaling pathway through miR-98-5p/HMGB1 axis. LncRNA OIP5-AS1 accelerates ox-LDL-induced endothelial cell injury through regulating HMGB1 mediated by miR-98-5p via the TLR4/NF-κB signaling pathway.

LncRNA OIP5‑AS1 aggravates house dust mite‑induced inflammatory responses in human bronchial epithelial cells via the miR‑143‑3p/HMGB1 axis.

Bronchial asthma poses a serious threat to human health. Previous studies have documented the role of long non-coding RNAs (lncRNAs) in asthma. However, the molecular mechanism underlying bronchial asthma remains unclear. The aim of the present study was to evaluate the role of the lncRNA Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) in the house dust mite-induced inflammatory response in human bronchial epithelial cells. BEAS-2B cells were treated with Dermatophagoides pteronyssinus peptidase 1 (Der p1) to establish an in vitro model of asthma. OIP5-AS1 expression levels increased in BEAS-2B cells following Der p1 treatment, while microRNA (miR)-143-3p was downregulated. Additionally, the levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin (IL)-6 and IL-8 were measured, and apoptosis was evaluated following OIP5 silencing. OIP5-AS1 knockdown reduced the inflammatory response and apoptosis in BEAS-2B cells. Furthermore, using dual luciferase reporter assays and co-transfection experiments, it was demonstrated that the function of OIP5-AS1 was mediated by miR-143-3p. miR-143-3p overexpression attenuated the Der p1-induced inflammatory response and apoptosis of BEAS-2B cells by targeting high mobility group box 1 (HMGB1). In summary, OIP5-AS1 exacerbated Der p1-induced inflammation and apoptosis in BEAS-2B cells by targeting miR-143-3p via HMGB1.

LncRNA OIP5-AS1 Promotes Breast Cancer Progression by Regulating miR-216a-5p/GLO1

BackgroundBreast cancer is a familiar malignant tumor, which is a great threat to women's life. Long noncoding RNA Opa interacting protein 5-antisense RNA 1 (OIP5-AS1) has been reported to be associated with numerous cancers. This study aimed to explore the role of OIP5-AS1 and the mechanism of its action in the progression of breast cancer. MethodsThe expression of OIP5-AS1 and miR-216a-5p was detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, or invasion was assessed by 4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, flow cytometry, or transwell assay, respectively. The binding sites were predicted by bioinformatics tool starBase2.0 (http://starbase.sysu.edu.cn/starbase2/index.php). The interaction between miR-216a-5p and OIP5-AS1 or glyoxalase 1 (GLO1) was confirmed by dual-luciferase reporter assay. The expression of GLO1 was quantified by Western blot. Nude mouse tumorigenicity assays were conducted to verify the role of OIP5-AS1 in vivo. ResultsOIP5-AS1 and GLO1 were highly expressed in both clinical tumor tissues and cell lines, whereas miR-216a-5p was downregulated. Knockdown of OIP5-AS1 suppressed proliferation, migration, and invasion but promoted apoptosis of breast cancer cells. MiR-216a-5p was a target of OIP5-AS1 and interacted with GLO1. MiR-216a-5p inhibition or GLO1 overexpression reversed the effects of OIP5-AS1 knockdown on the development of breast cancer cells. OIP5-AS1 knockdown depleted tumor growth in vivo. ConclusionsOIP5-AS1 knockdown suppressed the progression of breast cancer by inducing GLO1 expression via competitively binding to miR-216a-5p, suggesting that OIP5-AS1 was a hopeful biomarker for the therapy of breast cancer.

OIP5-AS1 modulates epigenetic regulator HDAC7 to enhance non-small cell lung cancer metastasis via miR-140-5p.

Long non-coding RNAs have been reported to be involved in non-small cell lung cancer (NSCLC) progression. However, whether Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) serves a role in NSCLC remains unclear. Bioinformatics analysis of The Cancer Genome Atlas datasets showed clinical significance and relevance of OIP5-AS1 in NSCLC. Western blotting and reverse transcription-quantitative PCR revealed protein and RNA expression levels of the genes [including OIP5-AS1, microRNA (miR)-140-5p, histone deacetylase 7 (HDAC7) and vascular endothelial growth factor A (VEGFA)]. Direct associations between the genes (miR-140-5p and OIP5-AS1, or miR-140-5p and HDAC7) were confirmed using a dual-luciferase reporter assay. Lymphatic vessel formation and invasion ability were detected using a lymphatic vessel formation assay and Transwell invasion assay. OIP5-AS1 knockdown attenuated lymphatic vessel length and invasion. The role of OIP5-AS1 was reverted by miR-140-5p. HDAC7 and VEGFA are downstream effectors of miR-140-5p-mediated NSCLC metastasis. OIP5-AS1, miR-140-5p, HDAC7 and VEGFA were all dysregulated in human clinical NSCLC tumor tissues. In conclusion, the present results demonstrated a novel mechanism for OIP5-AS1-induced metastatic phenotypes of NSCLC via the miR-140-5p/HDAC7/VEGFA axis.

Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma

Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) has been demonstrated to facilitate proliferation, metastasis and resistance to treatments in various types of cancers. Nevertheless, the exact mechanisms underlying the roles of OIP5-AS1 in osteosarcoma(OS) drug resistance have not yet been clearly elucidated. Therefore, we sought to investigate the functional involvement of OIP5-AS1 in osteosarcoma. Our results indicated that OIP5-AS1 was dramatically up-regulated in osteosarcoma drug-resistant tissues and cells in comparison with drug-sensitive tissues and cells. Also, the knockdown of OIP5-AS1 was found to have decreased doxorubicin resistance of OS cells. Further analyses revealed that OIP5-AS1 operated as a competitor for endogenous RNA of miR-137-3p as well as regulated pleiotrophin(PTN) expression, which has been reported to be an oncogene in OS in previous research. Furthermore, the loss of miR-137-3p or alternatively, the gain of PTN, both resulted in the abolishment of the inhibitory role of OIP5-AS1 silencing the proliferative activity. Our analyses indicated and helped to determine the role of OIP5-AS1 in contributing to tumorigenesis of osteosarcoma via the miR-137-3p/PTN axis and, therefore outlining its potential for use as a therapeutic target against this cancer.