Rab18 is a potential molecular biomarker for diagnosis and assessing the progression of human gliomas

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Rab18 is a potential molecular biomarker for diagnosis and assessing the progression of human gliomas

Basic Medicine | 更新时间：2026-01-09

- Rab18 is a potential molecular biomarker for diagnosis and assessing the progression of human gliomas
- Journal of Third Military Medical University Vol. 42, Issue 18, Pages: 1803-1808(2020)
- 作者机构：
  
  1.510515 广州，南方医科大学第一临床医学院
  2.430070 武汉，中国人民解放军中部战区总医院医学实验科
- 作者简介：
- 基金信息：
  
  Key Supporting Project of Health and Family Planning Commission of Hubei Province(WJ2017Z021)
- DOI：10.16016/j.1000-5404.202003269
  CLC： R341; R394.3; R730.264
- Received：21 March 2020，
  
  Revised：2020-05-31，
  
  Published：30 September 2020
- 稿件说明：
移动端阅览
Qili LUO, Yueping LIU, Zilin YUAN, et al. Rab18 is a potential molecular biomarker for diagnosis and assessing the progression of human gliomas[J]. Journal of Third Military Medical University, 2020, 42(18): 1803-1808.
DOI：

Qili LUO, Yueping LIU, Zilin YUAN, et al. Rab18 is a potential molecular biomarker for diagnosis and assessing the progression of human gliomas[J]. Journal of Third Military Medical University, 2020, 42(18): 1803-1808. DOI： 10.16016/j.1000-5404.202003269.

摘要

目的

2

通过沉默Rab18的方法探讨Rab18对人胶质瘤U87细胞增殖和凋亡的影响机制，进而初步验证Rab18表达水平在人胶质瘤诊断和进展的价值。

方法

2

将不转染的U87细胞作为空白对照组，转染NC siRNA和Rab18 siRNA的U87细胞分别作为阴性对照组和实验组；经手术切除获取瘤旁正常脑组织15例(

n

=15)和人胶质瘤组织33例(

n

=33)，所有患者术前未曾接受放化疗。分别采用qRT-PCR和Western blot检测Rab18和凋亡相关蛋白mRNA及蛋白的表达；CCK-8实验检测细胞增殖；流式细胞术检测细

胞周期和凋亡；HE染色后观察组织形态学。

结果

2

① 沉默Rab18后人胶质瘤U87细胞Rab18 mRNA和蛋白表达显著下调(

P

<

0.01)，不仅能使G

0

/G

1

期细胞显著增加伴随S期细胞显著减少(

P

<

0.01)，还能显著上调凋亡相关蛋白P53、Caspase 7、Bax及Bim mRNA和蛋白表达水平(

P

<

0.01)；②Rab18在人胶质瘤组织中mRNA和蛋白的表达水平显著高于瘤旁正常脑组织(

P

<

0.01)，且高级别胶质瘤(WHO Ⅲ~Ⅳ

n

=19)Rab18 mRNA和蛋白的表达水平显著高于低级别胶质瘤(WHOⅠ~Ⅱ

n

=14)(

P

<

0.01)。

结论

2

沉默Rab18不仅能抑制人胶质瘤细胞增殖，还能诱导其凋亡。且Rab18的表达水平与恶性程度有关。Rab18可作为人胶质瘤一个潜在的临床诊断和进展的分子标志物。

Abstract

Objective

2

To investigate the mechanism by which Rab18 affects proliferation and apoptosis of human glioma cells and assess the value of Rab18 as a biomarker for diagnosis and evaluating the progression of gliomas.

Methods

2

Human glioma U87 cells were transfected with a small interfering RNA (siRNA) targeting Rab18 or a negative control siRNA. The changes in mRNA and protein expression of Rab18 and apoptosis-related proteins were detected with qRT-PCR and Western blotting

and the cell proliferation was assessed using CCK-8 test; the changes in cell cycle and cell apoptosis were analyzed using flow cytometry. We also collected surgical specimens of human glioma tissues (

n

=33) and adjacent normal brain tissues (

n

=15) from patients who never received chemotherapy or radiotherapy prior to the surgery for histological examination with HE staining and analysis of Rab18 mRNA and protein expression in relation with the pathological grade of the tumors.

Results

2

The mRNA and protein expression levels of Rab18 were significantly downregulated in U87 cells after Rab18 silencing (

P

<

0.01)

which induced not only cell cycle arrest in G

0

/G

1

phase and reduced percentage of S phase cells (

P

<

0.01) but also upregulated the mRNA and protein expression levels of the apoptosis-related proteins P53

caspase7

Bax

and Bim (

P

<

0.01). In the surgical specimens

the gliomas expressed significantly higher levels of Rab18 than the adjacent tissues (

P

<

0.01)

and the expression levels of Rab18 were significantly higher in high-grade gliomas (WHO Ⅲ~Ⅳ

n

=19) than in the low-grade gliomas (WHO Ⅰ~Ⅱ

n

=14;

P

<

0.01).

Conclusion

2

Rab18 silencing not only inhibits cell proliferation but also promotes cell apoptosis in human glioma cells. Its expression level is related with the malignancy of the tumor

suggesting its value as a potential molecular biomarker for diagnosis and evaluating progression of human glioma.

关键词

Keywords

references

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MVLLER M P, GOODY R S. Molecular control of rab activity by GEFs, GAPs and GDI[J]. Small GTPases, 2018, 9(1/2): 5-21. DOI: 10.1080/21541248.2016.1276999.

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LIU J C, ZHANG J K, LI Y S, et al . MiR-455-5p Acts as a novel tumor suppressor in gastric cancer by down-regulating RAB18[J ] . Gene, 2016, 592(2): 308-315. DOI: 10.1016/j.gene.2016.07.034.

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YE F, TANG H L, LIU Q, et al . MiR-200b as a prognostic factor in breast cancer targets multiple members of RAB family[J ] . J Transl Med, 2014, 12: 17. DOI: 10.1186/1479-5876-12-17.

YAN W, ZHANG W, YOU G, et al . Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group[J ] . Neuro-oncology, 2 012, 14(12): 1432-1440. DOI: 10.1093/neuonc/nos263.

YANG S H, WANG S M, SYU J P, et al . Andrographolide induces apoptosis of C6 glioma cells via the ERK-p53-caspase 7-PARP pathway[J ] . Biomed Res Int, 2014, 2014: 312847. DOI: 10.1155/2014/312847.DOI: 10.1155/2014/312847

ZHAO L, FENG Y, SHI A W, et al . Apoptosis induced by microbubble-assisted acoustic cavitation in K562 cells: the predominant role of the cyclosporin A-dependent mitochondrial permeability transition pore[J ] . Ultrasound Med Biol, 2015, 41(10): 2755-2764. DOI: 10.1016/j.ultrasmedbio.2015.05.021.

WU QW, SUN X Q, YUE W H, et al . RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex[J ] . Mol Brain, 2016, 9: 19. DOI: 10.1186/s13041-016-0198-2.

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