MiRNA-218, a new regulator of HMGB1, suppresses cell migration and invasion in non-small cell lung cancer

Zhang, Cailian; Ge, Sheng-Li; Hu, Cailian; Yang, Ning; Zhang, Jin-Ran

doi:10.1093/abbs/gmt109

Cited by 60 publications

(56 citation statements)

References 32 publications

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“…It is well known that one miRNA may target many genes in different cell systems and miR-218 is no exception. There are several relatively common target genes of miR-218 in cancers such as BMI-1 [14, 27, 28], surviving [29-32] and HMGB1 [26, 33-36]. BMI-1 is a member of the polycomb group (PcG) of genes and is the first identified PcG transcriptional repressor.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

Yang

Cheng

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

Yang

Cheng

Zhang

et al. 2017

Cell Physiol Biochem

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“…It has been shown that miR-218 expression is downregulated in many tumors including ESCC (15)(16)(17)(18)(19)(20) and is involved in cancer initiation and development (15)(16)(17)(18)(19)(20)(21)(22) SOT (38), Rob1 receptor (39) as well as LAmb3 (40), which are involved in several different signaling pathways, suggesting that miR-218 is a tumor suppressor miRNA and plays a crucial role in the initiation, development and metastasis of tumors. Therefore, we reasonably speculated that miR-218 suppresses the tumor growth of ESCC in vitro and in vivo by regulating multiple target genes.…”

Section: Discussionmentioning

confidence: 99%

“…microRNA-218 (miR-218) is a recently discovered miRNA and is downregulated in several types of cancer, such as gastric cancer (15,16), cervical squamous cell carcinoma (17), medulloblastoma (18), lung cancer (19) and glioblastoma (20). Accumulating evidence demonstrates that miR-218 acts as a tumor suppressor and confers an inhibitory effect on cancer cell proliferation, migration and invasion by targeting genes (15)(16)(17)(18)(19)(20)(21)(22). In particular, recently studies have demonstrated that overexpression of miR-218 increased chemosensitivity to cisplatin (CDDP) in cervical cancer cells (23).…”

Section: Introductionmentioning

confidence: 99%

miR-218 suppresses tumor growth and enhances the chemosensitivity of esophageal squamous cell carcinoma to cisplatin

et al. 2014

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Abstract.A growing body of evidence suggests that microRNA-218 (miR-218) acts as a tumor suppressor and is involved in tumor progression, development and metastasis and confers sensitivity to certain chemotherapeutic drugs in several types of cancer. However, our knowledge concerning the exact roles played by miR-218 in esophageal squamous cell carcinoma (ESCC) and the underlying molecular mechanisms remain relatively unclear. Thus, the aims of this study were to detect the expression of miR-218 in human ESCC tissues and explore its effects on the biological features and chemosensitivity to cisplatin (CDDP) in an ESCC cell line (Eca109), so as to provide new insights for ESCC treatment. Here, we found increased expression of miR-218 in the ESCC tissues compared with that in the matched non-tumor tissues, and its expression level was correlated with key pathological characteristics including clinical stage, tumor depth and metastasis. We also found that enforced expression of miR-218 significantly decreased cell proliferation, colony formation, migration and invasion, induced cell apoptosis and arrested the cell cycle in the G0/G1 phase, as well as suppressed tumor growth in a nude mouse model. In addition, our results showed that miR-218 mimics increased the sensitivity to the antitumor effect of CDDP in the human Eca109 cells. Importantly, this study also showed that miR-218 regulated the expression of phosphorylated PI3K, AKT and mTOR, which may contribute to suppressed tumor growth of ESCC and enhanced sensitivity of ESCC cells. These findings suggest that miR-218 is a potential therapeutic agent for the treatment of ESCC.

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“…Recently, microRNA-325-3p [21] and MiRNA-218 [22], as the new regulators of HMGB1, regulated cell invasion and proliferation by targeting HMGB1 in non-small cell lung cancer. Zhang et al [23] found that HMGB1 and NF-kappaB p65 protein expression showed a positive correlation, and HMGB1 and NF-kappaB p65 expression might be related to non-small cell lung cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Zhang

Wang

et al. 2015

Tumor Biol.

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Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines. Firstly, we detected the expression levels of HMGB1 by by real-time PCR and western blotting analysis, and the results demonstrated that HMGB1 was much higher expressed in non-small cell lung cancer cell lines, including A549, SPC-1-1, NCI-2170, SK-MES-1, and NCI-H1299, compared with that of WI-38. Next, 5 μM of adriamycin (AMD), 20 μM of cisplatin (DDP), and 50 μM of methotrexate (MTX) were used to treat A549 cells and SPC-A-1 cells for 48 h. The results showed that treatment with chemotherapy drugs significantly increased the levels of HMGB1 in A549 cells and SPC-A-1 cells. Moreover, the expression levels of HMGB1 increased in a time-dependent manner being treated with DDP. Then, the endogenous HMGB1 expression was successfully interferred with shRNA specific to HMGB1 in A549 and SPC-A-1 cells, which was detected by western blotting analysis. Then, the cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells were treated with increasing concentrations of cisplatin for 24, 48, and 72 h; cell viability were analyzed by MTT assay; and IC50 values were calculated. The results demonstrated that the expression level of HMGB1 in A549/DDP cells was much higher than that of A549 cells; moreover, transfection with HMGB1 shRNA in A549/DDP cells decreased the IC50 value of cisplatin in A549/DDP cells. The expression levels of autophagy-related proteins beclin-1 and LC3-II were significantly higher in A549/DDP cells or the A549 cells treated with chemotherapeutic drugs, compared with that in A549 cells. However, interference with endogenous HMGB1 obviously suppressed autophagy-related proteins and increased cell apoptosis rate and the expression of cleaved caspase-3 in A549/DDP cells. All of the data suggested that interference with the endogenous HMGB1 significantly inhibited cell autophagy and increased cell apoptosis of A549/DDP cells. Thus, the study on the resistance of chemotherapy drugs would provide a theoretical reference for clinical treatment of non-small cell lung cancer.

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MiRNA-218, a new regulator of HMGB1, suppresses cell migration and invasion in non-small cell lung cancer

Cited by 60 publications

References 32 publications

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

miR-218 suppresses tumor growth and enhances the chemosensitivity of esophageal squamous cell carcinoma to cisplatin

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

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