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转录组分析确定ARHGAP家族是与膀胱癌中促肿瘤免疫浸润和纳米力学特征相关的新型生物标志物。

Transcriptomic Analysis Identified ARHGAP Family as a Novel Biomarker Associated With Tumor-Promoting Immune Infiltration and Nanomechanical Characteristics in Bladder Cancer.

作者信息

Yang Chen, Wu Siqi, Mou Zezhong, Zhou Quan, Zhang Zheyu, Chen Yiling, Ou Yuxi, Chen Xinan, Dai Xiyu, Xu Chenyang, Liu Na, Jiang Haowen

机构信息

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Front Cell Dev Biol. 2021 Jul 7;9:657219. doi: 10.3389/fcell.2021.657219. eCollection 2021.

DOI:10.3389/fcell.2021.657219
PMID:34307347
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8294098/
Abstract

Bladder cancer (BCa) is a common lethal urinary malignancy worldwide. The role of ARHGAP family genes in BCa and its association with immuno-microenvironment remain largely unknown. ARHGAP family expression and immune infiltration in BCa were analyzed by bioinformatics analysis. Then, we investigated cell proliferation, invasion, and migration and of the ARHGAP family. Furthermore, atomic force microscopy (AFM) was employed in measuring cellular mechanical properties of BCa cells. The results demonstrated that ARHGAP family genes correlate with a tumor-promoting microenvironment with a lower Th1/Th2 cell ratio, higher DC cell infiltration, higher Treg cell infiltration, and T-cell exhaustion phenotype. Silencing ARHGAP5, ARHGAP17, and ARHGAP24 suppressed BCa cell proliferation, migration, and metastasis. Knocking down of ARHGAPs in T24 cells caused a relatively higher Young's modulus and lower adhesive force and cell height. Taken together, ARHGAP family genes promote BCa progressing through establishing a tumor-promoting microenvironment and promoting cancer progression.

摘要

膀胱癌（BCa）是全球常见的致命性泌尿系统恶性肿瘤。ARHGAP家族基因在膀胱癌中的作用及其与免疫微环境的关联在很大程度上仍不清楚。通过生物信息学分析对ARHGAP家族在膀胱癌中的表达及免疫浸润情况进行了分析。然后，我们研究了ARHGAP家族对细胞增殖、侵袭和迁移的影响。此外，利用原子力显微镜（AFM）测量了膀胱癌细胞的细胞力学特性。结果表明，ARHGAP家族基因与促肿瘤微环境相关，其Th1/Th2细胞比例较低、树突状细胞浸润较高、调节性T细胞浸润较高以及T细胞耗竭表型。沉默ARHGAP5、ARHGAP17和ARHGAP24可抑制膀胱癌细胞的增殖、迁移和转移。在T24细胞中敲低ARHGAPs会导致相对较高的杨氏模量、较低的粘附力和细胞高度。综上所述，ARHGAP家族基因通过建立促肿瘤微环境和促进癌症进展来推动膀胱癌的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e0/8294098/d49b361eb811/fcell-09-657219-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e0/8294098/f8d90ddfcd05/fcell-09-657219-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e0/8294098/17909fab5c6e/fcell-09-657219-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e0/8294098/2c59710931ee/fcell-09-657219-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01e0/8294098/d49b361eb811/fcell-09-657219-g010.jpg

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