MicroRNA‑216b regulated proliferation and invasion of non‑small cell lung cancer by targeting SOX9

Liu, Sida; Han, Dongyi; Dai, Hui; Liu, Danwei; Wang, Zhi-Hao

doi:10.3892/ol.2018.8573

Cited by 16 publications

(17 citation statements)

References 47 publications

(33 reference statements)

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“…MiR-216b has been reported to be a tumor suppressor and have an important role in human cancer progression [39]. Dysregulated expression of miR-216b was found in cancer and may affect cancer cell proliferation and invasion through reciprocal action with other genes [40–42]. The present study exhibited the down-regulation of miR-216b-5p and the up-regulation of PNPO in IDC tissues.…”

Section: Discussionsupporting

confidence: 53%

Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

Ren

Guan

Zhang

et al. 2019

Aging

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Pyridoxine 5′-phosphate oxidase (PNPO) is a converting enzyme for an active form of vitamin B6. This study aims to evaluate the biological function and the regulatory mechanism of PNPO in human breast invasive ductal carcinoma (IDC). We unveiled for the first time that PNPO was upregulated in patients with IDC and was correlated with the overall survival of patients with metastasis at the later stages. Suppression of PNPO inhibited breast cancer cell proliferation, migration, invasion and colony formation, arrested cell cycle at the G2/M phase and induced cell apoptosis. PNPO was positively correlated with lncRNA MALAT1 which was negatively correlated with miR-216b-5p. PNPO was down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. A microRNA response element was found in both PNPO and MALAT1 transcripts for miR-216b-5p and the dual-luciferase reporter assay confirmed the binding of these transcripts. Knockdown of MALAT1 resulted in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs. Taken together, these results reveal the biological function and a regulatory mechanism of PNPO, in which the MALAT1/miR-216b-5p/PNPO axis may be important in IDC development. Targeting this axis may have therapeutic potential for breast cancer.

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Section: Discussionsupporting

confidence: 53%

Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

Ren

Guan

Zhang

et al. 2019

Aging

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“…Previous studies showed that miR-216b inhibited cell progression and promoted apoptosis by downregulating KRAS in pancreatic cancer and clear cell renal cell carcinoma,19,20 and JAK2/STAT3 signaling in colorectal cancer 21. MiR-216b also regulated proliferation and invasion of NSCLC by targeting SOX9 22. In this work, we found that FOXM1 level was upregulated in NSCLC tissues, and negatively correlated with the expression of miR-216b.…”

Section: Discussionmentioning

confidence: 53%

<p>MiR-216b suppresses cell proliferation, migration, invasion, and epithelial–mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer</p>

Wang¹,

Wang²,

Du³

et al. 2019

OTT

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Background/aims: MiR-216b and forkhead box M1 (FOXM1) were demonstrated to exert their biological effects on the development and progression of tumors. This study aimed to investigate the expression and role of miR-216b and FOXM1 in tissues and cell lines of non-small cell lung cancer (NSCLC). Methods: The expressions of miR-216b and FOXM1 in NSCLC tissues and cells were detected by qRT-PCR and Western blot analysis. Cell proliferation was measured by CCK-8 assay. Cell migration and invasion were confirmed by Transwell assay. Finally, the bioinformatics and dual-luciferase reporter assay were conducted to validate the relationship of miR-216b and FOXM1. Results: Compared with normal tissues and cells, the expression of miR-216b was obviously decreased in NSCLC tissues and cells. However, the expressions of FOXM1 mRNA and protein were significantly increased, and negatively correlated with the expression of miR-216b. Multivariate Cox’s regression analysis suggested that miR-216b or FOXM1 expression was an independent prognostic factor for patients with NSCLC. MiR-216b overexpression remarkably repressed cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of NSCLC cells. The bioinformatics and dual-luciferase reporter assay validated that the 3ʹ-untranslated region (3ʹ-UTR) of FOXM1 mRNA was indeed a direct target of FOXM1. In vitro, overexpression of FOXM1 partially eliminated inhibitory effects of miR-216b on cell proliferation, migration, and invasion, whereas inhibition of FOXM1 contributed to inhibitory effects mediated by miR-216b. Conclusion: MiR-216b inhibits cell proliferation, migration, invasion, and EMT by targeting the expression of FOXM1 in human NSCLC. These findings suggested a potential therapeutic role of miR-216b in patients of NSCLC.

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“…Further, overexpression of miR-216b suppressed NSCLC cell proliferation and invasion by targeting SOX9. Interestingly, the effects of miR-216b can be mimicked by siRNA against SOX9 [24]. Here, we found that SOX9 overexpression results in an increase in N-cadherin and vimentin expression and a decrease in E-cadherin and γ-catenin expression.…”

Section: Discussionmentioning

confidence: 64%

SOX9 drives the epithelial–mesenchymal transition in non-small-cell lung cancer through the Wnt/β-catenin pathway

Huang

Wei

et al. 2019

J Transl Med

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Background The distant metastasis of cancer cells is a risk factor for tumor lethality and poor prognosis in non-small-cell lung carcinoma (NSCLC). Increased SOX9 expression has been associated with clinical stage and poor prognosis in NSCLC, but the molecular mechanisms by which SOX9 promotes metastasis in NSCLC are still unknown. Methods The relationship between SOX9 expression and T, N, M classification was assessed using the χ 2 test and Spearman’s analysis in 142 immunohistochemically diagnosed specimens of NSCLC. We also generated SOX9-overexpression and SOX9-knockdown cells lines and their corresponding control cell lines by transfection with lentiviral constructs. In vivo assay, SOX9-overexpressing and SOX9-knockdown NSCLC cells were injected in zebrafish to examine distance metastasis. Gene set enrichment analysis (GSEA) was applied to analysis the correlation between SOX9 overexpression and Wnt/β-catenin pathway. Luciferase assay was used to check transcriptional activity of TCF/LEF and western blot and immunofluorescence was employed to detect β-catenin translocation in SOX9-overexpression, SOX9-knockdown and their corresponding control cell lines. Results We found that SOX9 overexpression correlates with the T, N and M stage significantly ( p = 0.03, 0.000, and 0.032 respectively) in 142 immunohistochemically diagnosed specimens of NSCLC. SOX9 overexpression was found to decrease the expression of the epithelial cell markers E-cadherin and γ-catenin and increase the expression of the mesenchymal cell markers N-cadherin and vimentin. An in vivo assay showed distant metastasis of the SOX9-overexpressing cells, which was not observed in the SOX9-knockdown cells. These findings indicate that SOX9 promotes distant metastasis by promoting EMT in NSCLC cells. GSEA showed that SOX9 overexpression was significantly correlated with the Wnt/β-catenin pathway which was corroborated by the expression of EMT-associated proteins in this pathway and its downstream target genes. SOX9 overexpression was also found to enhance the transcriptional activity of TCF/LEF, promote the nuclear translocation of β-catenin and increase the phosphorylation of GSK3β at Ser9. Further, inhibition of β-catenin suppressed the metastasis-promoting effects of SOX9 overexpression. Conclusions This study is the first to report that SOX9 is associated with clinical TNM stage and indicates that SOX9 promotes migration, invasion and the EMT process through the Wnt/β-catenin pathway.

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MicroRNA‑216b regulated proliferation and invasion of non‑small cell lung cancer by targeting SOX9

Cited by 16 publications

References 47 publications

Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

<p>MiR-216b suppresses cell proliferation, migration, invasion, and epithelial–mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer</p>

SOX9 drives the epithelial–mesenchymal transition in non-small-cell lung cancer through the Wnt/β-catenin pathway

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MicroRNA‑216b regulated proliferation and invasion of non‑small cell lung cancer by targeting SOX9

Cited by 16 publications

References 47 publications

Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

Pyridoxine 5′-phosphate oxidase is correlated with human breast invasive ductal carcinoma development

<p>MiR-216b suppresses cell proliferation, migration, invasion, and epithelial&ndash;mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer</p>

SOX9 drives the epithelial–mesenchymal transition in non-small-cell lung cancer through the Wnt/β-catenin pathway

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<p>MiR-216b suppresses cell proliferation, migration, invasion, and epithelial–mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer</p>