miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2

Objective: To investigate the expression of long non-coding RNA ZXF2 in lung adenocarcinoma tissues and its effect on cell proliferation, migration and invasion. Methods: Forty pairs of cancerous and adjacent non-cancerous lung adenocarcinoma specimens were collected for the studies. Quantitative real-time PCR was used to analyze the expression of ZXF2 in tumor tissues and adjacent normal tissues. The expression of ZXF2 was correlated with patients' clinico-pathological data. Molecular pathway controlled by ZXF2 was explored by using small interfering RNA (siRNA) technology. CCK-8 cell proliferation assay, flow cytometry analysis and transwell assays were used to evaluate cell proliferation, migration and invasion. Results: The expression of ZXF2 was 2 fold or higher in 27 out of 40 (67.5%) cases of lung adenocarcinoma specimens than that in non-cancerous tissues (P<0.05). The relative expression level of ZXF2 was positively correlated with tumor lymph node metastasis (χ²=8.485, P<0.05) and poor prognosis of the patients (p=0.0217). In order to explore the molecular mechanisms of ZXF2 mediated tumor progression, ZXF2 expression was inhibited by siRNA in A549 cells, a highly aggressive and metastatic lung adenocarcinoma cell line. We found that siRNA-ZXF2 treatment inhibited cell proliferation (P<0.01) leading to cell cycle arrest (P<0.01). The cell migration and invasion were suppressed by siRNA-ZXF2 treatment (P<0.01). Further biochemical studies revealed that the knockdown of ZXF2 led to down regulation of c-Myc signaling. Conclusion: ZXF2 was overexpressed in lung adenocarcinoma tissues and the high expression of ZXF was closely related to tumor progression through c-Myc related pathway. Given the fact that both ZXF2 and c-Myc are located in the same chromosome 8q24.2 loci, the potential interaction between ZXF2 and c-Myc might be a novel target for treatment of lung adenocarcinoma.

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“…The procedure was described previously [10]. In brief, in vitro cell migration was examined in Boyden chamber system.…”

Section: In Vitro Migration and Invasion Assaysmentioning

confidence: 99%

Overexpression of Long Non-Coding RNA ZXF2 Promotes Lung Adenocarcinoma Progression Through c-Myc Pathway

Yang

Wang

et al. 2015

Cell Physiol Biochem

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“…The oncogenic role of EZH2 has recently been documented in several types of cancer [18, 19, 49]. MiR-26a has been reported to suppress tumorgenesis by targeting EZH2 in several tumors [24, 50]. To explore whether EZH2 involved in the miR-26a-mediated function in docetaxel-resistant LAD cells, we detected the expression level of EZH2 in docetaxel-resistant LAD cells and parental cells.…”

Section: Discussionmentioning

confidence: 99%

MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2

Chen

Tao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD). However, chemoresistance remains a major impediment to clinical application of this agent. It has been presented that decreased miR-26a expression lead to cisplatin resistance and promoted growth and migration in human lung cancer. Enhancer of zeste homolog 2 (EZH2) is the target of miR-26a. The present study aimed to investigate the function of miR-26a/EZH2 in the acquisition of malignant behaviors of LAD. Methods: MiR-26a and EZH2 expression levels in the dcetaxel-insensitive groups (n = 19) and the docetaxel-sensitive groups (n = 18) were assessed by qRT-PCR. Colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays and western blotting were performed to assess the effects of miR-26a on proliferation, apoptosis and epithelial-to-mesenchymal (EMT) phenotypes in docetaxel resistant LAD cells in vitro. Xenograft transplantation, immunohistochemistry, tunel assays and western blotting assays were employed to demonstrate the role of miR-26a in docetaxel resistant LAD cells in vivo. The expression level of EZH2 in docetaxel-resistant LAD cells and corresponding parental cells was detected by qRT-PCR and western blotting. The relationship between miR-26a and EZH2 was confirmed by luciferase reporter assay. And rescue assays were performed to further confirm that miRNA-26a contributes to the acquisition of malignant behaviors of docetaxel-resistant LAD cells through targeting EZH2. Results: MiR-26a was significantly down-regulated in the dcetaxel-insensitive groups (n = 19) compared with the docetaxel-sensitive groups (n = 18) assessed by qRT-PCR. MiR-26a decreased the proliferation, increased the apoptosis rate and reversed EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro. EZH2 was confirmed as target of miR-26a. Rescue assays further verified that the function of miR-26a exerts in docetaxel-resistant LAD cells is through targeting EZH2. Conclusions: Our data revealed that overexpression of miR-26a in docetaxel-resistant LAD cells could decrease the proliferation, increase the apoptosis rate and reverse EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro and such function is partially exerted via downregulating EZH2. MiR-26a/EZH2 signal pathway makes contribute to the malignant phenotype of docetaxel-resistant of LAD cells which indicated that miR-26a exerts pivotal functions in the molecular etiology of chemoresistant lung adenocarcinoma.

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“…Other potential, functionally active miRNAs in NPC include miR26a [34,35] , miR-98 [36] , miR-155 [37,38] , miR-200a/b [39][40][41] , miR-205 [42,43] , and miR-216b [44] . Proposed targets of these miRNAs represent regulators of important processes such as the epithelial-to-mesenchymal transition (EMT) [39] , as well as signaling pathways including Notch [41] , phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-Akt [42] , and MAPK [44] .…”

Section: Human Mirna Expression In Npcmentioning

confidence: 99%

MicroRNAs in nasopharyngeal carcinoma

et al. 2016

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MicroRNAs (miRNAs) provide insight into both the biology and clinical behavior of many human cancers, including nasopharyngeal carcinoma (NPC). The dysregulation of miRNAs in NPC results in a variety of tumor-promoting effects. Furthermore, several miRNAs are prognostic markers for NPC. In addition to cellular miRNAs, NPC samples also often contain miRNAs encoded by Epstein-Barr virus, and these miRNAs may impact NPC biology by targeting both cellular and viral genes. Given their numerous putative roles in NPC development and progression, a thorough understanding of the impact of miRNA dysregulation in NPC is expected to shed light on useful biomarkers and therapeutic targets for the clinical management of this disease. In this review, we describe the efforts to date to identify and characterize such miRNAs in the context of NPC.

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miR-26a inhibits invasion and metastasis of nasopharyngeal cancer by targeting EZH2

Cited by 75 publications

References 21 publications

Overexpression of Long Non-Coding RNA ZXF2 Promotes Lung Adenocarcinoma Progression Through c-Myc Pathway

Overexpression of Long Non-Coding RNA ZXF2 Promotes Lung Adenocarcinoma Progression Through c-Myc Pathway

MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2

MicroRNAs in nasopharyngeal carcinoma

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