MicroRNA-26a regulates tumorigenic properties of EZH2 in human lung carcinoma cells

Dang, Xiaomin; Ma, Aiqun; Yang, Lan; Hu, Hao; Zhu, Bo; Shang, Dong; Chen, Tianjun; Luo, Yukun

doi:10.1016/j.cancergen.2012.01.002

Cited by 84 publications

(69 citation statements)

References 49 publications

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“…These data suggest that the Ezh2 gene plays a role in promoting the proliferation of glioma cells. Consistent with our findings, previous studies have also shown that the Ezh2 gene promotes the proliferation of lung (18), breast (9), thyroid (19), colon (20), ovarian (21), and pancreatic cancer cells (22). Therefore, we concluded that the Ezh2 gene plays an important role in the regulation of the proliferation of glioma cells.…”

Section: Discussionsupporting

confidence: 92%

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells

Zhang¹,

Wang²,

Chang³

et al. 2012

Oncology Reports

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Abstract. The Ezh2 gene is an important member of the polycomb-group (PcG) family. As a newly identified oncogene, the expression of Ezh2 has been shown to be significantly increased in prostate cancer, breast cancer, renal cell carcinoma and hepatic cancer; however, a role for Ezh2 in the occurrence of glioma has not yet been reported. In this study, we found that the Ezh2 gene is highly expressed in U87 human glioma cells. Using RNA interference, we demonstrated that the downregulation of Ezh2 expression in U87 human glioma cells resulted in apoptosis and a cell cycle arrest in the G0/G1 phase. In addition, we found that silencing of the Ezh2 gene altered the mitochondrial membrane potential and promoted the release of cytochrome c from the mitochondria. Furthermore, the reduced expression of Ezh2 altered the Bax and Bcl-2 protein levels and led to the activation of caspase 9 and 3. These results indicate that the apoptosis induced in U87 human glioma cells by the silencing of the Ezh2 gene is related to the mitochondrial pathway.

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Section: Discussionsupporting

confidence: 92%

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells

Zhang¹,

Wang²,

Chang³

et al. 2012

Oncology Reports

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“…It has been reported that miR-26a is involved in various malignant pathological processes and acts as a tumor suppressor to inhibit tumor cell proliferation by directly targeting EZH2 in pancreatic, nasopharyngeal, breast, and lung cancer. [32][33][34][35] In addition, clinical studies showed that patients with higher level of miR26a in tumor tissues have better prognosis, possibly through the role of miR-26a in inhibition of cell proliferation via targeting cyclin D2, cyclin E2, and IL-6. 36,37 Our results suggest that miR-26a acts through arresting G1-S transition to suppress A549 cell proliferation, and this effect is mediated by HMGA2-E2F1-Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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Background: Lung cancer is the most common cancer that is caused by perturbation of regulatory pathways rather than dysfunction of a single gene. Cisplatin (CDDP; cis-diamminedichloroplatinum II) is the first member of a class of platinum-containing anti-cancer medication, which binds to DNA and triggers apoptosis. CDDP-based chemotherapy is used to treat various types of cancers. However, the efficacy of CDDP in the treatment of non-small-cell lung cancer (NSCLC) is limited by acquired drug resistance. MicroRNAs have recently emerged as key regulators of cancers, and miR-26a is one of downregulated miRNAs in A549/CDDP res cell line. This study aimed to investigate the role of miR-26a in CDDP resistance in NSCLC as well as the underlying mechanisms.Methods: In this study, we analyzed expressional profiles of CDDP resistance-related mRNA, miRNA, and transcription factors (TF) that regulate miRNA expression in NSCLC. A549 cells were treated with CDDP, miR-26a mimic, or miR-26a inhibitor, and followed by biological analysis including drug sensitivity assay, colony formation assay, terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay, and cell cycle analysis. Luciferase assay was used to determine the target of miR-26a. The regulation of miR-26a in Akt pathway was measured by western blot.Results: High mobility group A (HMGA) 2 was identified as the target of miR-26a. Overexpression of miR26a in A549 cells inhibited G1-S transition, increased cell death in response to CDDP treatment, and decreased the colony formation of A549 cells. MiR-26a significantly decreased the expression of E2F1, diminished Akt phosphorylation, and downregulated Bcl2 expression. Cell growth was suppressed by inhibiting HMGA2-mediated E2F1-Akt pathway.Conclusion: MiR-26a is responsible for A549 cell sensitivity in the treatment of CDDP through regulating HMGA2-mediated E2F1-Akt pathway.

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“…71 Furthermore, EZH2 mediates epigenetic silencing of the promoters of DAB2IP, a crucial inhibitory modulator of oncogenic Ras-mediated signaling, which ultimately promotes tumor growth and induces metastasis in prostate cancer cell lines. [72][73][74][75] In anaplastic thyroid cancer cell lines, EZH2 directly prevents cell growth inhibition and differentiation by silencing the thyroidspecific transcription factor paired box gene 8 (PAX8).…”

Section: Commentmentioning

confidence: 99%

Enhancer of Zeste Homolog 2 Expression Is Associated With Metastasis and Adverse Clinical Outcome in Clear Cell Renal Cell Carcinoma: A Comparative Study and Review of the Literature

Abourbih

Sircar

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase mediating chromatin condensation and epigenetic modulation, is overexpressed in various human carcinomas and is associated with adverse clinicopathologic characteristics and biologic behavior. The expression of EZH2 in renal cell carcinomas (RCCs) has not been fully characterized yet.Objective.-To evaluate the prognostic role of EZH2 in RCC by analyzing the immunohistochemical staining pattern of the marker in relation to pathologic features and clinical outcome.Design.-We correlated the immunolabeling of EZH2 with multiple clinicopathologic features, including Fuhrman nuclear grade, pathologic stage, metastatic status, and clinical outcome in 223 clear cell RCCs (CRCCs) and 21 papillary RCCs, by using tissue microarrays of primary and metastatic cases.Results.-Most CRCCs (75%) showed positive EZH2 staining, with most primary tumors showing focal staining in comparison to nonfocal staining in metastatic cases. In primary tumors, EZH2 expression was associated with higher nuclear grade and lower pathologic stage. Metastatic tumors showed a higher number of positive cases (81% versus 67%) and a more diffuse and more intense pattern of staining than primary CRCCs. For the 22 locally advanced primary tumors (T3/4) and 43 metastatic RCCs, patients who experienced RCC-related deaths significantly overexpressed the marker in comparison to patients who did not experience RCC-related mortality.Conclusions.-By showing that EZH2 expression is associated with increased metastatic potential and a worse clinical outcome, this study suggests that EZH2 can serve as a prognostic biomarker for RCC, thus confirming it as a key molecule driving oncogenesis and metastasis.

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MicroRNA-26a regulates tumorigenic properties of EZH2 in human lung carcinoma cells

Cited by 84 publications

References 49 publications

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Enhancer of Zeste Homolog 2 Expression Is Associated With Metastasis and Adverse Clinical Outcome in Clear Cell Renal Cell Carcinoma: A Comparative Study and Review of the Literature

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