Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

Zm, Shi; Wang, L; Shen, Hua; Cf, Jiang; Ge, Xianping; Dm, Li; Wen, Yu; Hr, Sun; Mh, Pan; Li, Wei; Yq, Shu; Liu, Lingzhi; Sc, Peiper; He, Jun; Jiang, Bing-Hua

doi:10.1038/onc.2016.414

Cited by 134 publications

(110 citation statements)

References 62 publications

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“…Previous studies have suggested that several miRNAs were abnormal expression in the progress of periodontal disease and regulated multifarious genes such as RUNX2, osteocalcin (OC), and EGFR (Motedayyen, Ghotloo, Saffari, Sattari, & Amid, ; Xie et al, ; Zhou et al, ). MiR‐218, a tumour suppressor, is significantly downregulated in various cancers (Deng et al, ; Shi et al, ) and inflammatory disorders (Xu et al, ). For example, the decrease of serum miR‐218 levels was observed in the inflammation induced by cigarette smoking, and miR‐218 overexpression would repress TNFR1‐mediated activation of NF‐κB and resulted in decreasing levels of serum IL‐6 and IL‐8 (Xu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Section: Mir-218 Decreased Bone Destruction and Inflammation In Ligmentioning

confidence: 99%

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Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

Guo

Zeng

Miao

et al. 2019

Cellular Microbiology

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Periodontitis is a multiple infection and inflammatory disease featured by connective tissue homeostasis loss, periodontal inflammation, and alveolar bone resorption. MicroRNAs (miRNAs) are involved in the mediation of a large scale of pathological processes. Here, we show that miRNA‐218 provides protective effect on periodontitis via regulation of matrix metalloproteinase‐9 (Mmp9). This pathway is aberrant in periodontium from rats with periodontitis and human periodontal ligament progenitor cells stimulated by lipopolysaccharide, with downregulation of miR‐218 and higher levels of Mmp9 compared with periodontium from healthy rats and cells without stimulation. Overexpression of miR‐218 can suppress the degradation of Collagen Types I and IV and dentin sialoprotein (DSP), attenuate osteoclast formation, and inhibit the secretion of proinflammatory cytokines. On the other hand, overexpression of Mmp9 promotes the degradation of Collagen Types I and IV and DSP as well as RANKL‐induced osteoclast formation and elevates inflammatory factors levels. Furthermore, the inhibitory effect of miR‐218 was prevented by rescuing the Mmp9 expression. In addition, we also have showed that miR‐218 was able to attenuate bone resorption and inflammation in a periodontitis rat model. Collectively, our findings therefore suggest that miR‐218 acts as a protective role in periodontitis through the regulation of Mmp9.

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Section: Discussionmentioning

confidence: 99%

Section: Mir-218 Decreased Bone Destruction and Inflammation In Ligmentioning

confidence: 99%

Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

Guo

Zeng

Miao

et al. 2019

Cellular Microbiology

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“…14,15 MicroRNAs, such as miR-494, miR-153 and miR-218, inhibited lung cancer development and metastasis via suppressing cellular proliferation, inhibiting cell migration and invasion and EMT. [16][17][18] Here, we found that B3GNT3 was overexpressed in lung cancer and upregulated expression of B3GNT3 was associated with unfavorable prognosis of lung cancer patients. Silencing B3GNT3 inhibited lung cancer cell growth in vitro and suppressed lung tumor development in vivo.…”

Section: Introductionmentioning

confidence: 73%

<p>B3GNT3, a Direct Target of miR-149-5p, Promotes Lung Cancer Development and Indicates Poor Prognosis of Lung Cancer</p>

Sun¹,

Liu²,

Lu³

et al. 2020

CMAR

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These authors contributed equally to this work Background: B3GNT3 (β1, 3-N-acetylglucosaminyltransferase-3) belongs to the β3GlcNAcT family and is essential to form extended core 1 oligosaccharides. Previous studies revealed that B3GNT3 expression was dysregulated in multiple cancers. Here, we aimed to understand the expression profile and function of B3GNT3 in lung cancer. Materials and Methods: The expression of B3GNT3 was measured by immunohistochemistry and public database analysis. B3GNT3 was knocked down to evaluate the lung cancer cell proliferation, migration and invasion in in vitro and in vivo tumor formation experiments. miR-149-5p targeting B3GNT3 was identified with TargetScan analysis and confirmed with reporter assay. Overexpression of miR-149-5p was achieved using microRNA mimics and function of microRNA-149-5p/B3GNT3 axis was tested in vitro. Results: B3GNT3 was upregulated in lung cancer, and B3GNT3 overexpression was associated with poor prognosis of lung cancer patients. High expression of B3GNT3 was associated with advanced TNM stages, larger tumor size, tumor metastasis and recurrence. Functionally, we demonstrated that knockdown of B3GNT3 suppressed lung cancer cell growth and invasion in vitro. Knockdown of B3GNT3 suppressed lung cancer development in a xenograft tumor model. Moreover, miR-149-5p was validated to negatively regulate B3GNT3 expression through directly targeting B3GNT3 3ʹ-UTR. Overexpression of miR-149-5p could antagonize the tumorigenesis effect of B3GNT3 in vitro. Conclusion: In summary, our study demonstrated that B3GNT3 overexpression was correlated with poor prognosis of lung cancer patient, indicating that B3GNT3 could be a promising prognostic biomarker for lung cancer. miR-149-5p negatively regulated B3GNT3 expression, which might be utilized for therapeutic target in lung cancer.

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“…MiR-218 has been widely reported to be silenced in multiple human cancers, and function as a putative tumor suppressor, including gastric, nasopharyngeal, lung, cervical, oral and brain tumors [9][10][11][35][36][37][38][39]. Besides, glioma patients with low miR-218 expression had poorer disease-free survival and overall survival [12].…”

Section: Discussionmentioning

confidence: 99%

MiR-218 inhibits malignant phenotypes of glioma by targeting TNC/AKT/AP-1/TGFβ1 feedback signaling loop

Dang

Zhang

Tian

et al. 2020

Preprint

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Background: Gliomas are the most common and malignant tumors in the brain of humans, and the prognosis of glioma patient is very poor. MicroRNAs (miRNAs) play critical roles in different types of cancer by regulating gene expression at the posttranscriptional levels. Although miR-218 has been reported to be downregulated in gliomas, its role in gliomas still remains largely unknown.Methods: MiR-218 expression in gliomas and normal brain tissues (control subjects) were analyzed using TCGA dataset. The biological roles of miR-218 in glioma cells were determined by a series of in vitro and in vivo studies. The dual-luciferase reporter system was performed to identify potential targets of miR-218. The regulatory effect of miR-218 on TNC/AKT/AP-1/TGFβ1 pathway was evaluated by dual-luciferase reporter system and western blot. Results:We demonstrated miR-218 was significantly downregulated in gliomas compared to control subjects, and exerted a potent tumor suppressor in glioma cells by inhibiting cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice, as well as inducing cell cycle arrest and apoptosis.Mechanistically, miR-218 inhibited malignant phenotypes of glioma cells by binding to the 3' UTR of its target TNC and subsequently repressing its expression. As a result, it could reduce AKT phosphorylation and subsequently inhibit transcriptional activity of AP-1 by reducing JNK phosphorylation, downregulating the expression of TGFβ1, while TGFβ1 is able to, in turn, activate the TNC/AKT/AP-1 signaling axis. Conclusions:Our data uncover a previously unknown tumor suppressor role of miR-218 in glioma by blocking the TNC/AKT/AP-1/TGFβ1 positive feedback loop. BackgroundGliomas are the most common and malignant tumors in the brain of humans, which represent about 70% of all brain tumors [1]. The current standard of care for newly diagnosed gliomas patients includes maximal safe surgical resection, followed by a combination of radiation and chemotherapy [2,3]. However, despite these treatment, overall survival rate of the patients suffering from glioma is among the lowest of all the main types of cancer and has not improved during recent decades [4].

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Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

Cited by 134 publications

References 62 publications

Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

<p>B3GNT3, a Direct Target of miR-149-5p, Promotes Lung Cancer Development and Indicates Poor Prognosis of Lung Cancer</p>

MiR-218 inhibits malignant phenotypes of glioma by targeting TNC/AKT/AP-1/TGFβ1 feedback signaling loop

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