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

转录组分析确定 ARHGAP 家族是与膀胱癌促进肿瘤的免疫浸润和纳米机械特性相关的新型生物标志物

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

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 in vivo and in vitro 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.

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