Long noncoding RNA AC003092.1 promotes temozolomide chemosensitivity through miR-195/TFPI-2 signaling modulation in glioblastoma

Xu, Ningbo; Liu, Boyang; Lian, Changlin; Doycheva, Desislava; Zhao, Fen; Liu, Yanting; Zhou, Jian; He, Zhenyan; Zhao, Yang; Huang, Qiongzhen; Zeng, Huijun

doi:10.1038/s41419-018-1183-8

Cited by 68 publications

(43 citation statements)

References 53 publications

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“…LncRNAs GAS5, NEAT1, GACAT3, CASC9, HMMR-AS1, LINC00152, HOTAIRM1, AC003092.1, HOXD-AS1, OIP5-AS1, DANCR and so on have been reported to play oncogenic or tumour suppressive roles in glioma. 32,33,[41][42][43][44][45][46][47][48][49] Our study further proved the critical roles of lncRNAs in glioma and provided another candidate lncRNA for glioma prognosis and therapy. Multi-centre analyses of the correlation between LINC00526 expression and prognosis of glioma patients would further detect the potential of LINC00526 as a prognostic biomarker, which needs further investigation.…”

Section: Discussionsupporting

confidence: 56%

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Yan

et al. 2019

J Cellular Molecular Medi

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Glioma is the most common primary intracranial carcinoma with extremely poor prognosis. The significances of long non‐coding RNA (lncRNA) involved in glioma have been started revealed. However, the expression, roles and molecular mechanisms of most lncRNAs in glioma are still unknown. In this study, we identified a novel lncRNA LINC00526, which is significantly low expressed in glioma. Low expression of LINC00526 is correlated with aggravation and poor survival in glioma. Functional assays revealed that ectopic expression of LINC00526 inhibits glioma cell proliferation, migration, and invasion. LINC00526 silencing promotes glioma cell proliferation, migration and invasion. Mechanistically, we found that LINC00526 directly interacts with EZH2, represses the binding of EZH2 to AXL promoter, attenuates the transcriptional activating roles of EZH2 on AXL , and therefore represses AXL expression. Via repressing AXL, LINC00526 further represses PI3K/Akt/NF‐κB signalling. Intriguingly, we identified that NFKB1 and NFKB2 directly binds LINC00526 promoter and represses LINC00526 transcription. We further found that via activating NF‐κB signalling, AXL represses LINC00526 transcription. Therefore, LINC00526/EZH2/AXL/PI3K/Akt/NF‐κB form a feedback loop in glioma. Analysis of the TCGA data revealed that the expression of LINC00526 is inversely correlated with that of AXL in glioma tissues. In addition, functional rescue assays revealed that the tumour suppressive roles of LINC00526 are dependent on the negative regulation of AXL. Collectively, our data identified LINC00526 as a tumour suppressor in glioma via forming a double negative feedback loop with AXL. Our data also suggested LINC00526 as a potential prognostic biomarker and therapeutic candidate for glioma.

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Section: Discussionsupporting

confidence: 56%

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Yan

et al. 2019

J Cellular Molecular Medi

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“…demonstrated that miR‐130a was subjected to epigenetic silencing in hemangioma, which consequently ameliorated the malignancy through targeting TFPI‐2 via the FAK/PI3K/Rac1/mdm2 signaling cascade. In addition, the study performed by Xu et al . showed that lncRNA AC003092.1 improved chemosensitivity to temozolomide by modulating the miR‐195/TFPI‐2 pathway in glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Geng

Liu

et al. 2020

The Journal of Gene Medicine

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Background:The tumor suppressor role of tissue factor pathway inhibitor 2 (TFPI-2) has been reported in various tumors. The present study aimed to improve the understanding of the oncogenic properties of TFPI-2 in gastric cancer. Methods:Relative expression of TFPI-2 was determined by a real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell viability was measured via a cell counting kit-8 assay and proliferation was evaluated by a colony formation assay. Cell apoptosis was assessed with a caspase-3 activity kit and invasion was evaluated by a transwell chamber assay. The methylation level of TFPI-2 promoter was assayed by methylation-specific PCR. The regulatory effect of miR-27a-3p on TFPI-2 was analyzed with a luciferase reporter assay. The direct association between miR-27a-3p and TFPI-2 was shown by biotin-labelling pulldown.Results: TFPI-2 was down-regulated in gastric cancer, which associated with an unfavorable prognosis clinically. Ectopic introduction of TFPI-2 greatly compromised cell viability, colony formation and invasive capacity, and also induced cell apoptosis simultaneously. The promoter region of TFPI-2 was extensively methylated in gastric cancer tissues compared to normal tissues, suggesting the epigenetic inhibition of TFPI-2 expression. We further identified that TFPI-2 functioned as sponge RNA against miR-27a-3p. Most importantly, miR-27a-3p-specific inhibitor significantly exerted a tumor suppressor function akin to TFPI-2 itself, and the anti-tumoral activities were completely abolished by TFPI-2 knockdown. Conclusions:We found that the epigenetically suppressed TFPI-2 compromised sponging effects with respect to miR-27a-3p in gastric cancer, which consequently and mechanistically contributed to the tumor biology of gastric cancer. K E Y W O R D Sgastric cancer, methylation, miR-27a-3p, TFPI-2 Geng and Liu contributed equally to this work.

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“…As is known to all, in ceRNA mechanism, lncRNAs could competitively bind with miRNAs, thus positively regulating the target genes of miRNAs. [13][14][15] In these F I G U R E 3 F11-AS1 regulated PTEN expression by competitively binding with miR-3146. A, RT-qPCR of PTEN in cells transfected with miR-3146 mimics and miR-3146 mimics+pcDNA3.1/F11-AS1.…”

Section: F11-as1 Regulates Pten Expression By Competitively Bindingmentioning

confidence: 97%

LncRNA F11‐AS1 suppresses liver hepatocellular carcinoma progression by competitively binding with miR‐3146 to regulate PTEN expression

Chen

Liu

et al. 2019

J of Cellular Biochemistry

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Accumulating evidence has proved that long noncoding RNAs (lncRNAs) are involved in cancer progression. The abnormal expression of lncRNAs might mediate cancer in various ways. Liver hepatocellular carcinoma (LIHC) is the third leading cause of tumor‐related deaths. Due to the difficulty in its early recognition, the therapeutic outcomes of LIHC are far from satisfactory. The lncRNA Coagulation Factor XI Antisense RNA 1 (F11‐AS1) is underexpressed in LIHC and suppresses LIHC progression in return. F11‐AS1 can bind with and negatively regulate miR‐3146, while miR‐3146 can bind with and negatively regulate PTEN. Moreover, F11‐AS1 positively regulates the messenger RNA and protein level of PTEN. Also, miR‐3146, F11‐AS1, and PTEN could all be immunoprecipitated by antibody against Ago2, indicating the existence of RNA–induced silencing complex. Therefore, F11‐AS1 mediates PTEN expression by acting as competing endogenous RNA of miR‐3146. Further rescue assays demonstrated that F11‐AS1 suppressed LIHC progression via such pattern. To sum up, F11‐AS1 suppresses LIHC progression by competitively binding with miR‐3146 to regulate PTEN expression. The F11‐AS1/miR‐3146/PTEN axis is brand new. Taken together, the results indicate that F11‐AS1 might serve as a therapeutic target of LIHC.

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Long noncoding RNA AC003092.1 promotes temozolomide chemosensitivity through miR-195/TFPI-2 signaling modulation in glioblastoma

Cited by 68 publications

References 53 publications

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Long non‐coding RNA LINC00526 represses glioma progression via forming a double negative feedback loop with AXL

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

LncRNA F11‐AS1 suppresses liver hepatocellular carcinoma progression by competitively binding with miR‐3146 to regulate PTEN expression

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