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LINC00452 promotes ovarian carcinogenesis through increasing ROCK1 by sponging miR-501-3p and suppressing ubiquitin-mediated degradation.

ABSTRACT: Ovarian cancer refers to all sorts of cancerous growth that starts from the ovary. Dysregulation of long non-coding RNAs (lncRNAs) is associated with ovarian cancer development and progression. Cellular expression and localization of LINC00452 in ovarian cancer cells were detected by qPCR and FISH. The roles of LINC00452 in ovarian carcinogenesis were characterized by MTT, transwell and colony-formation assays in vitro as well as xenograft mouse model. The underlying mechanism was explored by microarray, RIP, Co-IP and luciferase reporter assays. This study identified a novel lncRNA LINC00452 being elevated in both ovarian cancer cells and tumor tissues in patients. Such aberrant expression of LINC00452 was negatively correlated with relapse-free survival of ovarian cancer patients. Overexpression of LINC00452 potentiated CaOV3 cell viability, migration and invasion in vitro as well as xenograft tumor growth in vivo. Evidence from the current study suggests that the carcinogenicity of LINC00452 is partially due to competitive sponging of miR-501-3p followed with release of repression on the ROCK1, a key effector in Rho signaling pathway. Irrespective of its miRNA sponge function, LINC00452 is capable of preventing ROCK1 protein from ubiquitin/proteasome-mediated degradation via their mutual physical interaction. Our study makes LINC00452 a potential therapeutic target for ovarian cancer.

SUBMITTER: Yang J

PROVIDER: S-EPMC7695380 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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LINC00452 promotes ovarian carcinogenesis through increasing ROCK1 by sponging miR-501-3p and suppressing ubiquitin-mediated degradation.

Yang Juan J Wang Wei-Gang WG Zhang Ke-Qiang KQ

Aging 20201109 21

Ovarian cancer refers to all sorts of cancerous growth that starts from the ovary. Dysregulation of long non-coding RNAs (lncRNAs) is associated with ovarian cancer development and progression. Cellular expression and localization of LINC00452 in ovarian cancer cells were detected by qPCR and FISH. The roles of LINC00452 in ovarian carcinogenesis were characterized by MTT, transwell and colony-formation assays <i>in vitro</i> as well as xenograft mouse model. The underlying mechanism was explore ...[more]

PMID: 33168781

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Project description:ObjectivesThis research aims to verify that the long non-coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC.Materials and methodsFirstly, qRT-PCR was used to detect the expression of genes including LncRNA DANCR and miR-27a-3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual-luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh-NC and sh-DANCR to detect proliferation and SMMC-7721 cells stably transfected with sh-NC and sh-DANCR to investigate metastasis.ResultsThe results of qRT-PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh-DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR-27a-3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR-27a-3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR-27a-3p axis regulates EMT progression by cell immunofluorescence and Western blot.ConclusionsIn a word, DANCR promotes HCC development and induces EMT by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway.

Project description:BackgroundLong noncoding RNA (lncRNA) LINC00922 has been reported to promote tumorigenesis of lung and breast cancer. However, the functions and mechanisms of LINC00922 in ovarian cancer (OC) remain unclarified. The current study aims to clarify the detailed functions and underlying mechanisms of LINC00922 in the progression of OC.MethodsLINC00922 expression in OC tissues and cells was identified by a comprehensive strategy of data miming, computational biology and quantitative real-time polymerase chain reaction (RT-qPCR) experiment. In vitro CCK-8, wound healing, transwell invasion, western blotting and in vivo tumorigenesis assays LINC00922 were conducted to evaluate the functions of LINC00992. Subsequently, bioinformatics technology and dual luciferase reporter assay were performed to confirm the between miR-361-3p and LINC00922 or CLDN1. Finally, rescue experiments were performed to confirm whether LINC00922 effect functions of OC cells through regulation of miR-361-3p.ResultsLINC00922 was significantly upregulated in OC tissues and cell lines, which is significantly positively corelated with the poor prognosis of patients with OC. LINC00922 knockdown inhibited proliferation and tumorigenesis of OC cells in vitro and vivo. In addition, LINC00922 knockdown suppressed migration, invasion, and EMT of OC cells in vitro. Mechanically, LINC00922 could competitively bind with miR-361-3p to relieve the repressive effect of miR-361-3p on its target gene CLDN1 in OC cells. In addition, silencing miR-361-3p promoted OC cell proliferation, migration, invasion, EMT and Wnt/β-catenin signaling, while LINC00922 knockdown inhibited Wnt/β-catenin signaling by upregulating miR-361-3p. Rescue experiments revealed that LINC00922 knockdown inhibited OC cell proliferation, migration, invasion and EMT by regulating miR-361-3p.ConclusionThis study suggested that LINC00922 could competitively bind with miR-361-3p to promote the CLDN1 expression and activate Wnt/β-catenin signaling in OC progression, which providing a promising therapeutically target for OC.

Project description:BackgroundLong noncoding RNAs (lncRNAs) have been reported to play a key role in the development and progression of human malignancies. FLJ33360 is an lncRNA with unknown functions. This study was designed to determine the clinical significance and mechanism of FLJ33360 in ovarian cancer.Materials and methodsThe clinical significance of FLJ33360 in ovarian cancer was determined using the Gene Expression Profiling Interactive Analysis (GEPIA) database, Kaplan-Meier Plotter database, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and statistical analysis. The regulatory relationships between FLJ33360 and miR-30b-3p were explored through bioinformatics, the Gene Expression Omnibus (GEO) database, the ArrayExpress database and meta-analysis. The possible pathways were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the key target genes were identified using a protein-protein interaction (PPI) network, the Cancer Genome Atlas (TCGA) database, and correlation analysis.ResultsFLJ33360 expression was significantly downregulated in ovarian cancer tissue (P=0.0011) and was closely associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.027) and recurrence (P=0.002). FLJ33360 may have potential value in detecting ovarian cancer (area under the curve =0.793). Function analysis demonstrated that FLJ33360 can act as a molecular sponge of miR-30b-3p to regulate the expression of target genes that are mainly involved in positive regulation of smooth muscle cell migration, the unsaturated fatty acid metabolic process, and positive regulation of the epithelial to mesenchymal transition. Among these target genes, BCL2 is the hub gene.ConclusionFLJ33360 is a potential biomarker for early diagnosis and prognostic assessment in ovarian cancer and may regulate the expression of genes by sponging miR-30b-3p and thus participate in the development of ovarian cancer.

Dataset Information

LINC00452 promotes ovarian carcinogenesis through increasing ROCK1 by sponging miR-501-3p and suppressing ubiquitin-mediated degradation.

Publications

LINC00452 promotes ovarian carcinogenesis through increasing ROCK1 by sponging miR-501-3p and suppressing ubiquitin-mediated degradation.

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