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RAS Promotes Proliferation and Resistances to Apoptosis in Meningioma

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Abstract

In this study, we investigated the influence of elevated RAS expression on the growth of meningioma in vivo and in vitro. The IOMM-LEE cells, representing a cell line derived from malignant meningioma, were divided into blank control group (cells without any drug treatment), negative control group (cells treated with an equal volume of normal saline to replace drug), and farnesyl thiosalicylic acid (FTS)-treated group (cells treated with FTS). Methyl-thiazole-tetrazolium bromide (MTT) assay and flow cytometer (with cells after FTS (75 μmol/L) treatment for 48 h) were utilized to determine the proliferation and apoptosis, respectively, of IOMM-LEE cells after RAS inhibition. Western blot analysis was used for semi-quantitative analysis of p-ERK and p-AKT levels. Animal model of human meningioma was established with sub-renal capsule transplantation, and mice were divided into two groups: experimental group (50 mg/kg group, 75 mg/kg group, and 100 mg/kg, hypodermic injection with FTS) and control group. Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (IHC). Western blot analysis was used for detecting ERK and AKT signal pathway. The proliferation of IOMM-LEE cells decreased dramatically and apoptosis rate increased significantly in FTS-treated group compared to blank control group and negative control group (all P < 0.05). At FTS concentration of 75 μmol/L, the apoptosis rate of IOMM-LEE cells reduced significantly over time (P < 0.05). Cell cycle analysis showed that IOMM-LEE cells exhibited G1-arrest in the FTS-treated group, compared to no cell-cycle arrest in blank control group and the negative control group (P < 0.05). Further, significantly decreased ERK and AKT phosphorylation levels were detected in IOMM-Lee cells after FTS (75 μmol/L) treatment for 48 h, compared to blank control group and negative control group (P < 0.05). The results in vivo experiments showed that after FTS treatment, tumor volume, PCNA LI, and the levels of p-ERK and p-Akt decreased significantly in 75 mg/kg group and 100 mg/kg group when compared with the control group and 50 mg/kg group (all P < 0.05). Our findings provide strong evidence that RAS protein is highly expressed in meningioma cells, and the RAS activity is inhibited by downregulating ERK and AKT signal pathway, which may further inhibit the growth of meningioma.

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Acknowledgments

This study was supported by the Science and Technology Project of Jiangxi (number 20141BBG70050), National Natural Science Foundation of People’s Republic of China (Nos. 81302187, 81200644), cws14c063. We would like to acknowledge the reviewers for their helpful comments on this paper.

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Authors and Affiliations

  1. Department of Radiation Oncology, Nanchang University, Nanchang, 330006, China

    Chunling Jiang

  2. Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, 330029, China

    Chunling Jiang, Jingao Li, Fan Ao & Xiaochang Gong

  3. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410000, China

    Tao Song

  4. Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Military University, No 440 North Chengdu Road, Huangpu District, Shanghai, 200003, China

    Yicheng Lu, Chenran Zhang & Hua He

  5. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China

    Liangyu Chen & Yunhui Liu

  6. Key Laboratory of Women’s Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, No 318 Bayi Avenue, Nanchang, 330006, China

    Ouping Huang

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  1. Chunling Jiang
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  2. Tao Song
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  3. Jingao Li
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  4. Fan Ao
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  10. Hua He
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Correspondence to Hua He or Ouping Huang.

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The authors declare that they have no competing interests.

Additional information

Dr. Ouping Huang [ouping_huang@126.com] is the first corresponding author.

Chunling Jiang and Tao Song contributed equally as co-first author to this work.

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Jiang, C., Song, T., Li, J. et al. RAS Promotes Proliferation and Resistances to Apoptosis in Meningioma. Mol Neurobiol 54, 779–787 (2017). https://doi.org/10.1007/s12035-016-9763-z

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  • DOI: https://doi.org/10.1007/s12035-016-9763-z

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