Dataset Information

Long non-coding RNA LINC01535 promotes cervical cancer progression via targeting the miR-214/EZH2 feedback loop.

ABSTRACT: Long non-coding RNAs (lncRNAs) have shown critical roles in multiple cancers via competitively binding common microRNAs. miR-214 has been proved to play tumour suppressive roles in various cancers, including cervical cancer. In this study, we identified that lncRNA LINC01535 physically binds miR-214, relieves the repressive roles of miR-214 on its target EZH2, and therefore up-regulates EZH2 protein expression. Intriguingly, we also found that EZH2 directly represses the expression of miR-214. Thus, miR-214 and EZH2 form double negative regulatory loop. Through up-regulating EZH2, LINC01535 further represses miR-214 expression. Functional experiments showed that enhanced expression of LINC01535 promotes cervical cancer cell growth, migration and invasion in vitro and cervical cancer xenograft growth in vivo. Reciprocally, LINC01535 knockdown suppresses cervical cancer cell growth, migration and invasion. Activation of the miR-214/EZH2 regulatory loop by overexpression of miR-214 or silencing of EZH2 reverses the roles of LINC01535 in promoting cervical canc`er cell growth, migration and invasion in vitro and cervical cancer xenograft growth in vivo. Clinically, LINC01535 is significantly up-regulated in cervical cancer tissues and correlated with advanced clinical stage and poor prognosis. Moreover, the expression of LINC01535 is reversely associated with the expression of miR-214 and positively associated with the expression of EZH2 in cervical cancer tissues. In conclusion, this study reveals that LINC01535 promotes cervical cancer progression via repressing the miR-214/EZH2 regulatory loop.

SUBMITTER: Song H

PROVIDER: S-EPMC6714211 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long non-coding RNA LINC01535 promotes cervical cancer progression via targeting the miR-214/EZH2 feedback loop.

Song Hongjuan H Liu Yuan Y Jin Xin X Liu Yang Y Yang Yanling Y Li Lei L Wang Xuan X Li Guilin G

Journal of cellular and molecular medicine 20190705 9

Long non-coding RNAs (lncRNAs) have shown critical roles in multiple cancers via competitively binding common microRNAs. miR-214 has been proved to play tumour suppressive roles in various cancers, including cervical cancer. In this study, we identified that lncRNA LINC01535 physically binds miR-214, relieves the repressive roles of miR-214 on its target EZH2, and therefore up-regulates EZH2 protein expression. Intriguingly, we also found that EZH2 directly represses the expression of miR-214. T ...[more]

PMID: 31273925

Similar Datasets

Project description:BackgroundThough androgen deprivation therapy is the standard treatment for prostate cancer (PCa), most patients would inevitably progress to castration-resistant prostate cancer (CRPC) which is the main cause of PCa death. Therefore, the identification of novel molecular mechanism regulating cancer progression and achievement of new insight into target therapy would be necessary for improving the benefits of PCa patients. This study aims to study the function and regulatory mechanism of HOTAIR/EZH2/miR-193a feedback loop in PCa progression.MethodsMSKCC and TCGA datasets were used to identify miR-193a expression profile in PCa. Cell Counting Kit-8 (CCK-8) assays, colony formation, invasion, migration, flow cytometry, a xenograft model and Gene Set Enrichment Analysis were used to detect and analyze the biological function of miR-193a. Then, we assessed the role of HOTAIR and EZH2 in regulation of miR-193a expression by using plasmid, lentivirus and small interfering RNA (siRNA). Luciferase reporter assays and chromatin immunoprecipitation assays were performed to detect the transcriptional activation of miR-193a by EZH2 and HOTAIR. Further, qRT-PCR and luciferase reporter assays were conducted to examine the regulatory role of miR-193a controlling the HOTAIR expression in PCa. Finally, the correlation between HOTAIR, EZH2 and miR-193a expression were analyzed using In situ hybridization and immunohistochemistry.ResultsWe found that miR-193a was significantly downregulated in metastatic PCa through mining MSKCC and TCGA datasets. In vitro studies revealed that miR-193a inhibited PCa cell growth, suppressed migration and invasion, and promoted apoptosis; in vivo results demonstrated that overexpression of miR-193a mediated by lentivirus dramatically reduced PCa xenograft tumor growth. Importantly, we found EZH2 coupled with HOTAIR to repress miR-193a expression through trimethylation of H3K27 at miR-193a promoter in PC3 and DU145 cells. Interestingly, further evidence illustrated that miR-193a directly targets HOTAIR showing as significantly reduced HOTAIR level in miR-193a overexpressed cells and tissues. The expression level of miR-193a was inversely associated with that of HOTAIR and EZH2 in PCa.ConclusionThis study firstly demonstrated that miR-193a acted as tumor suppressor in CRPC and the autoregulatory feedback loop of HOTAIR/EZH2/miR-193a served an important mechanism in PCa development. Targeting this aberrantly activated feedback loop may provide a potential therapeutic strategy.

Project description:BackgroundAngiogenesis and metastasis contributes substantially to the poor outcome of patients with ovarian cancer. We aimed to explore the role and mechanisms of the long non-coding RNA NEAT1 (nuclear enriched abundant transcript 1) in regulating angiogenesis and metastasis of human ovarian cancer. NEAT1 expression in human ovarian cancer tissues and cell lines including SKOV-3 and A2780 was investigated through in situ hybridization. Gene knockdown and overexpressing were achieved through lentivirus infection, transfection of plasmids or microRNA mimics. Cell viability was measured with the cell counting kit-8 assay, while apoptosis was determined by flow cytometry. Cell migration and invasion were evaluated by transwell experiments, and protein expression was determined by western blot assays or immunohistochemistry. Duo-luciferase reporter assay was employed to confirm the interaction between NEAT1 and target microRNA. In vivo tumor growth was evaluated in nude mice with xenografted SKOV-3/A2780 cells, and blood vessel formation in tumor was examined by histological staining.ResultsNEAT1 was highly expressed in ovarian cancer tissues of patients and cell lines. MiR-214-3p was identified as a sponging target of NEAT1, and they antagonizedeach other in a reciprocal manner. NEAT1-overexpressing SKOV-3 and A2780 cells had significantly increased proliferation, reduced apoptosis, and augmented abilities of migration and invasion, while cells with NEAT1-knockdown displayed markedly attenuated traits of malignancies. Additionally, the levels of NEAT1 appeared to be positively correlated with the expression levels of angiogenesis-related molecules, including Semaphorin 4D (Sema4D), Sema4D receptor Plexin B1, T-lymphoma invasion and metastasis-inducing protein-1 (Tiam1), and Rho-like GTPases Rac1/2/3. In the xenograft mouse model, more NEAT1 expression resulted in faster in vivo tumor growth, more blood vessel formation in tumor tissues, as well as higher expression levels of angiogenesis-related molecules and CD31.ConclusionsNEAT1 promotes angiogenesis and metastasis in human ovarian cancer. NEAT1 and miR-214-3p are promising targets for developing therapeutics to treat human ovarian cancer.

Dataset Information

Long non-coding RNA LINC01535 promotes cervical cancer progression via targeting the miR-214/EZH2 feedback loop.

Publications

Long non-coding RNA LINC01535 promotes cervical cancer progression via targeting the miR-214/EZH2 feedback loop.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets