Knockdown of lncRNA ZNRD1-AS1 suppresses gastric cancer cell proliferation and metastasis by targeting the miR-9-5p/HSP90AA1 axis.
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ABSTRACT:
SUBMITTER: Ba MC
PROVIDER: S-EPMC8312431 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nasopharyngeal carcinoma (NPC) is often associated with the infection of Epstein-Barr virus in nasopharynx and is mainly happened in South China and Southeast Asia. Recently, noncoding RNAs have been reported to regulate NPC carcinogenesis. LncRNA OIP5-AS1 participates in tumorigenesis and progression; however, the inherent mechanism of OIP5-AS1-mediated progression of NPC is unclear. In the current study, we aimed to explore the role of OIP5-AS1 in NPC progression. We measured the cell viability, apoptosis, migration, and invasion in NPC cells after OIP5-AS1 modulation. Moreover, we determined whether OIP5-AS1 exerts its oncogenic functions via sponging miR-183-5p in NPC. Furthermore, we determined whether glutamate ammonia ligase (GLUL) was a downstream target of miR-183-5p. We found that OIP5-AS1 downregulation inhibited the viability, migration and invasion of NPC via targeting miR-183-5p. We also identified that GLUL might be a potential downstream target of miR-183-5p in NPC cells. Mechanistically, OIP5-AS1 promotes cell motility via regulating miR-183-5p and GLUL in NPC cells. We concluded that OIP5-AS1 performed its biological functions via targeting miR-183-5p and GLUL in NPC cells.
| S-EPMC9214031 | biostudies-literature
Project description:BackgroundZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. However, the relationship between ZNRD1-AS1 and retinoblastoma has not been studied in detail. This study aimed to determine the role of ZNRD1-AS1 in retinoblastoma.MethodsDifferentially expressed genes in retinoblastoma downloaded from GEO database were identified by Limma package, and the expression and cell location of ZNRD1-AS1 were detected by real-time quantitative PCR (RT-qPCR). The relationships between miR-128-3p and two genes (ZNRD1-AS1 and BMI1) were analyzed by bioinformatics and dual-luciferase assay. After manipulating the expressions of ZNRD1-AS1, miR-128-3p and BMI1, cell viability, tube length, migration, invasion and the protein expressions (PCNA, E-Cadherin, N-Cadherin) of retinoblastoma cells were determined by cell counting kit-8 (CCK-8), tube formation, transwell and Western blot assays, respectively. Subcutaneous transplantation tumor assay, immunohistochemistry, and RT-qPCR were applied to verify the functions of the target gene in vivo.ResultsZNRD1-AS1 was up-regulated in the cytoplasm of retinoblastoma and regulated BMI1 via sponging miR-128-3p. ZNRD1-AS1 knockdown alleviated the malignant phenotype (viability, tube length, migration and invasion) of retinoblastoma cells, reduced tumor volume and weight, and inhibited BMI1 and CD34 expressions. Different from miR-128-3p mimic, miR-128-3p inhibitor promoted malignant phenotype of retinoblastoma cells, and partially reversed the inhibitory effect of siZNRD1-AS1. MiR-128-3p mimic down-regulated BMI1, PNCA, N-Cadherin expressions, and up-regulated p16 and E-Cadherin expressions. The regulatory effect of miR-128-3p was partially reversed by BMI1.ConclusionZNRD1-AS1, acting as a "sponge" of miR-128-3p, up-regulates BMI1, thereby promoting the progression of retinoblastoma.
| S-EPMC8290669 | biostudies-literature
Project description:BackgroundMicroRNA 942-5p (miR-942-5p) has been reported to promote migration and invasion in non-small cell lung cancer (NSCLC), but the underlying mechanism is not completely understood. The interplay between long non-coding RNAs (lncRNAs) and miRNAs plays a crucial role in tumor progression.MethodsIn the present study, we performed bioinformatic and biochemical analyses to identify miR-942-5p-interacting lncRNAs. The function and clinical significance of the candidate lncRNA(s) in NSCLC were determined.ResultsWe identified LIFR-AS1 as a pivotal miR-942-5p-interacting lncRNA. Overexpression of miR-942-5p caused a reduction of LIFR-AS1 in NSCLC cells. LIFR-AS1 showed the ability to sponge miR-942-5p, leading to derepression of ZNF471. Functionally, LIFR-AS1 overexpression inhibited NSCLC cell migration and invasion, whereas LIFR-AS1 silencing yielded an opposite effect. In vivo studies confirmed that LIFR-AS1 overexpression suppressed lung metastasis of NSCLC cells. Rescue experiments demonstrated that enforced expression of miR-942-5p or depletion of ZNF471 restored the migration and invasion capacity of LIFR-AS1-overexpressing cells. Moreover, overexpression of ZNF471 restrained NSCLC cell invasion. Clinically, LIFR-AS1 downregulation was significantly correlated with TNM stage, lymph node metastasis, and reduced overall survival in NSCLC patients.Conclusionswe provide first evidence for the involvement of the LIFR-AS1/miR-942-5p/ZNF471 axis in NSCLC invasion and metastasis. LIFR-AS1 may represent a novel target for the treatment of NSCLC.
| S-EPMC7245777 | biostudies-literature
Project description:BackgroundThe incidence and mortality of thyroid cancer (TC) has been steadily rising in the past decades. It is imperative to have a better understanding of the molecular mechanisms underlying TC development and identify novel therapeutic targets. This study characterized the role of lncRNA CALML3-AS1 (CALML3-AS1) in the development of papillary thyroid cancer (PTC).MethodRelated mRNAs expression were validated in the tumor and adjacent normal tissues from 52 PTC patients and PTC cell lines by qRT-PCR. Expression of RBM38 was detected by Western blot. We have also conducted CCK-8 and colony formation assays were used to detect the effect of CALML3-AS1 on cell proliferation, Transwell assay was utilized to evaluate cell migration and invasion, apoptosis detected by flow cytometry assay, RNA pull-down and luciferase assays were performed to validate gene predictions.ResultsThe results indicated that the expression of both CALML3A-S1 and RBM38 were significantly downregulated in PTC tissues (p < 0.01), while the expression of miR-20a-5p was increased in PTC (p < 0.01). Functionally, CALML3-AS1 overexpression inhibited PTC cell proliferation in vitro and in vivo. Mechanistically, CALML 3-AS1 sponged miR-20a-5p, which in turn leads to the suppression of RBM38 expression and PTC progression.ConclusionsCALML3-AS1 functions as a ceRNA for miR-20a-5p in the regulation of the expression of RBM38 in PTC. Higher level of CALML3-AS1 serves as a good prognostic indicator of survival in PTC patients. Targeting CALML3-AS1/ miR-20a-5p/RBM38 axis may represent a novel therapeutic strategy in the treatment of PTC.
| S-EPMC8966157 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) are known as key regulators in many cancer types, but their biological functions in nasopharyngeal carcinoma (NPC) remain largely unknown. In the present study, we aim to explore the role of the lncRNA ZNRD1-AS1 in NPC tumor development.MethodsThe role of ZNRD1-AS1 in NPC tissues and cells was explored by using quantitative real-time PCR assay. Cellular behavioral experiments were used in testing NPC cell proliferation, invasion, and migration. Luciferase reporter assay, RNA-binding protein immunoprecipitation, and Western blot analysis were used in estimating the associations among ZNRD1-AS1, miR-335, and ROCK1.ResultsZNRD1-AS1 expression was elevated in the NPC tissues and cells, and ZNRD1-AS1 overexpression was positively correlated with advanced TNM stage and the presence of lymph node metastasis. Our biological experiments indicated that ZNRD1-AS1 knockdown reduces NPC cell invasion and metastasis. Further analyses revealed that ZNRD1-AS1 as a ceRNA promotes the migration and invasion of NPC cells by sponging miR-335. We provided evidence that ZNRD1-AS1 facilitates the invasion and metastasis of NPC cells via the miR-335-ROCK1 axis.ConclusionOur data shed light on the oncogenic role of ZNRD1-AS1 in NPC tumor development, and a promising therapeutic target for NPC was identified.
| S-EPMC7263878 | biostudies-literature
Project description:The lncRNAs have been made certain to take part in the development of most cancers in multiple ways. Here, our purpose is to making observation of the biological role and function of lncRNA CDKN2B-AS1 in human breast cancer. Twenty-eight pairs of breast cancer tissue and adjacent normal tissue from breast cancer patients were used to investigate the expression of CDKN2B-AS1 by qRT-PCR. And a lentivirus-shRNA guided CDKN2B-AS1 were to reduce its expression. The function of CDKN2B-AS1 was analyzed using a series of in vitro assays. Meanwhile, the xenograft model was used to further explicate the role of CDKN2B-AS1 in breast cancer. As for the results, there is a relative rich expression of CDKN2B-AS1 in breast cancer tissues compared with the corresponding adjacent normal tissues. Compared with the human breast epithelial cell line, the abundant expression of CDKN2B-AS1 in breast cancer cells were revealed as well. Then, knockdown CDKN2B-AS1 inhibited the malignant biological behaviors of MCF7 and T47D cells. In mechanism, CDKN2B-AS1 sponged the miR-122-5p to regulate STK39 expression. Furthermore, the inhibition effect with sh-CDKN2B-AS1 on breast cancer cells was alleviated by miR-122-5p inhibitor. Last, an in vivo model also confirmed that knockdown CDKN2B-AS1 retarded the growth of breast cancer. Our data concluded that knockdown of CDKN2B-AS1 suppresses the progression of breast cancer by miR-122-5p/STK39 axis.
| S-EPMC8806778 | biostudies-literature
Project description:Circular RNAs (circRNAs) are considered as a new regulatory factor in growth, metastasis and therapeutic resistance of human cancers. But the clinical significance and underlying mechanism of circular RNA ITCH (circ-ITCH) in gastric cancer (GC) remain unknown. In the present study, we found that circ-ITCH was down-regulated in GC cell lines, GC tissues and their serum-derived exosomes. The level of circ-ITCH was related to invasion depth. Functional assays showed that circ-ITCH overexpression inhibited the proliferation, migration, invasion and epithelial mesenchymal transition (EMT) of GC cells, whereas circ-ITCH knockdown appeared an opposite effect. Bioinformatic analysis and luciferase reporter assay confirmed that circ-ITCH acted as miR-199a-5p sponge and increased the level of Klotho. The expression level of miR-199-5p was up-regulated in GC tissues and negatively correlated with that of circ-ITCH. MiR-199a-5p mimics reversed the effects on inhibiting metastasis induced by circ-ITCH overexpression and decreased the level of Klotho in GC cells. Our findings indicate that circ-ITCH suppresses metastasis of GC by acting as the sponge of miR-199a-5p and increasing Klotho expression, which serves as a potential biomarker and targets for the diagnosis and therapy of GC.Abbreviations: CircRNAs: circular RNAs; GC: gastric cancer; circ-ITCH: circular RNA Itchy E3 ubiquitin protein ligase; ceRNA: competitive endogenous RNA; EMT: Epithelial-mesenchymal transition; siRNA: Small interfering RNA; TEM: transmission electron microscope; NTA: nanoparticle tracking analysis.
| S-EPMC8018440 | 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:Background:Long noncoding RNA X inactivate-specific transcript (lncRNA XIST) has been identified to contribute to the development and progression of non-small cell lung cancer (NSCLC). Thus, it is important to explore more specific functions and molecular mechanisms of XIST in NSCLC tumorigenesis. Materials and Methods:The expression of XIST, microRNA (miR)-142-5p and paired box 6 (PAX6) was measured using quantitative real-time polymerase chain reaction or Western blot, respectively. Cell proliferation was analyzed using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to measure apoptotic cells. Cell migration and invasion were determined by Transwell assay. The interaction between miR-142-5p and XIST or PAX6 was confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo experiments were performed through the murine xenograft model. Results:XIST was elevated in NSCLC, and XIST knockdown suppressed cell proliferation, migration, invasion and induced apoptosis in vitro as well as repressed tumor growth in vivo. MiR-142-5p was a target of XIST, and silencing miR-142-5p reversed the anti-tumor functions mediated by XIST knockdown in NSCLC cells. PAX6 was confirmed to be a target of miR-142-5p, and the inhibitory effects caused by miR-142-5p restoration in NSCLC cell malignant phenotypes were attenuated by PAX6 overexpression. Besides that, XIST could indirectly regulate PAX6 expression by sponging miR-142-5p in vivo and in vitro. Conclusion:XIST suppresses cell tumorigenicity in human NSCLC by regulating miR-142-5p/PAX6 axis, which indicates a novel insight into the pathogenesis of NSCLC and lays a foundation for the molecular therapy of NSCLC.
| S-EPMC7276200 | biostudies-literature
Project description:Background/aimsLong noncoding RNAs (lncRNAs) play a critical role in tumorigenesis and progression of ovarian cancer (OC). This study focused on the function and potential mechanism toward LEMD1-AS1 (LEMD1 antisense RNA 1) in the progression of ovarian cancer.Materials and methodsThe expression of LEMD1-AS1 in OC tissues was evaluated in TCGA and Gene Expression Omnibus datasets (GSE119056) and confirmed in OC cell lines via qRT-PCR (quantitative real-time polymerase chain reaction). Then, the location of LEMD1-AS1 in the cytoplasmic and nuclear RNAs extracted from OV cells was detected by qRT-PCR. Cell Counting Kit-8 (CCK-8), colony formation, wound-healing and transwell assays were applied to examine cell viability, proliferation, migration and invasion, respectively. Further, the effect of LEMD1-AS1 on OC tumor growth was determined via subcutaneous xenotransplanted tumor model. The potential target for LEMD1-AS1 was validated via dual-luciferase activity assay, RNA pull-down and RNA immunoprecipitation.ResultsThe expression of LEMD1-AS1 was decreased in OC tissues and cell lines. Forced overexpression of LEMD1-AS1 inhibited the proliferation, migration and invasion of ovarian cancer cells and transplanted tumor growth in nude mice. We found that LEMD1-AS1 was mainly located in the cytoplasm of OC cells and contained complementary sites of miR-183-5p. Mechanistically, our results showed that LEMD1-AS1 could directly interact with miR-183-5p and tumor protein p53 (TP53). The anti-tumor role of LEMD1-AS1 on OC progression depended on miR-183-5p-mediated TP53 expression.ConclusionLEMD1-AS1 suppresses OC progression through sponging miR-183-5p and regulation of TP53, suggesting a novel biomarker and target for OC.
| S-EPMC7395824 | biostudies-literature