TMEM9 promotes the proliferation and invasion of prostate cancer by affecting autophagy

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TMEM9 promotes the proliferation and invasion of prostate cancer by affecting autophagy

Basic research | 更新时间：2025-10-21

- TMEM9 promotes the proliferation and invasion of prostate cancer by affecting autophagy
- Journal of Chongqing Medical University Vol. 50, Issue 9, Pages: 1281-1289(2025)
- 作者机构：
  
  重庆医科大学附属第一医院泌尿外科，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003897
  CLC： R737.25
- Received：31 December 2024，
  
  Revised：2025-03-25，
  
  Accepted：13 May 2025，
  
  Published：28 September 2025
- 稿件说明：
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朱辉轩,苏帅,张金栋,等.TMEM9通过影响自噬促进前列腺癌增殖及侵袭[J].重庆医科大学学报,2025,50(9):1281-1289.

Zhu Huixuan,Su Shuai,Zhang Jindong,et al.TMEM9 promotes the proliferation and invasion of prostate cancer by affecting autophagy[J].Journal of Chongqing Medical University,2025,50(9):1281-1289.
朱辉轩,苏帅,张金栋,等.TMEM9通过影响自噬促进前列腺癌增殖及侵袭[J].重庆医科大学学报,2025,50(9):1281-1289. DOI： 10.13406/j.cnki.cyxb.003897.

Zhu Huixuan,Su Shuai,Zhang Jindong,et al.TMEM9 promotes the proliferation and invasion of prostate cancer by affecting autophagy[J].Journal of Chongqing Medical University,2025,50(9):1281-1289. DOI： 10.13406/j.cnki.cyxb.003897.

摘要

目的

2

探讨跨膜蛋白9（transmembrane protein 9，TMEM9）作为促癌基因在前列腺癌（prostate cancer，PCa）中的表达情况，并通过干预其表达探究对PCa细胞增殖、侵袭的影响，以及对Wnt/β-catenin信号通路及PCa细胞自噬的影响。

方法

2

采用癌症基因组图谱泛癌分析TMEM9在不同肿瘤中表达水平，临床PCa和前列腺增生标本中分析TMEM9的蛋白和信使核糖核酸（messenger ribonucleic acid，mRNA）水平。实时荧光定量聚合酶链式反应和蛋白质免疫印记分析TMEM9在不同PCa细胞系中的表达水平。细胞计数实验分析细胞增殖，TUNEL染色分析凋亡，Transwell检测PCa的侵袭。裸鼠皮下成瘤分析肿瘤体内增殖情况。蛋白质免疫印记分析自噬相关通路蛋白的表达情况，透射电子显微镜和免疫荧光共定位检测自噬小体和溶酶体细胞共定位。

结果

2

TMEM9在PCa中高表达。PCa组织中TMEM9的mRNA和蛋白水平的表达高于前列腺增生组织。TMEM9在PC3细胞（人PCa细胞）中表达量最高（

t

=17.150，

P

<

0.01），敲低TMEM9的PC3细胞增殖（

t

=3.165，

P

<

0.05）、侵袭（

F

=76.620，

P

<

0.01）明显减弱，凋亡率明显增高（

t

=13.530，

P

<

0.01）。敲低TMEM9后裸鼠皮下肿瘤的体积减小（

F

=1 699.000，

P

<

0.01），质量减轻（

t

=9.057，

P

<

0.01），肿瘤生长受抑制。TMEM9可调控Wnt/β-catenin信号通路并抑制AKT-mTOR信号通路来促进PCa自噬。

结论

2

TMEM9抑制AKT-mTOR信号通路通过自噬促进PCa细胞的增殖和侵袭。

Abstract

Objective

2

To explore the expression of transmembrane protein 9 （TMEM9） as an oncogene in prostate cancer （PCa），and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.

Methods

2

The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expression levels in different tumors，and TMEM9 protein and messenger ribonucleic acid （mRNA） levels in clinical PCa and prostatic hyperplasia specimens were analyzed. Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines. Cell counting，terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL），and Transwell assay were used to analyze cell proliferation，apoptosis，and PCa cell invasion，respectively. Subcutaneous tumorigenesis in nude mice was used to analyze tumor proliferation

in vivo

. Western blotting was used to analyze the expression of autophagy-related pathway proteins，and transmission electron microscopy and

immunofluorescence colocalization were used to determine the colocalization of autophagosomes and lysosomes.

Results

2

TMEM9 was highly expressed in PCa. The mRNA and protein expression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues. The expression of TMEM9 was highest in PC3 cells（human PCa cells）（

t

=17.150，

P

<

0.01）. In TMEM9-knocked down PC3 cells，the proliferation（

t

=3.165，

P

<

0.05） and invasion（

F

=76.620，

P

<

0.01） significantly decreased，and apoptosis（

t

=13.530，

P

=0.010） significantly increased. After knockdown of TMEM9，the volume（

F

=1 699.000，

P

<

0.01） and weight（

t

=9.057，

P

<

0.01） of subcutaneous tumors in nude mice were reduced，and tumor growth was inhibited. TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.

Conclusion

2

TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

关键词

Keywords

references

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