Mao Xiaoliang, Tong Jichun
Department of Thoracic Surgery, Yanghu Branch, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou, China,
Onco Targets Ther. 2018 Oct 24;11:7447-7457. doi: 10.2147/OTT.S175255. eCollection 2018.
Rho GTPase-activating protein 30 (ARHGAP30), a member of the Rho GTPase-activating proteins (Rho GAPs) family, plays an important role in the regulation of cytoskeleton organization and cell adhesion.
mRNA and protein expression was assessed by quantitative real-time PCR and Western blotting, respectively. Cell Counting Kit-8 (CCK-8) and Transwell assays were conducted to detect cell proliferation, migration, and invasion.
ARHGAP30 expression was downregulated in specimens and cell lines of lung cancer in comparison to non-cancerous specimens and normal bronchial epithelial cell lines, respectively. Moreover, in vitro experiments demonstrated that ARHGAP30 overexpression impeded the proliferative, migratory, and invasive abilities of lung cancer cells. Moreover, bioinformatics analysis with The Cancer Genome Atlas (TCGA) lung cancer dataset showed a negative association between ARHGAP30 expression and the Wnt signaling pathway. Enforced expression of ARHGAP30 decreased the mRNA and protein levels of β-catenin, c-Myc, matrix metalloproteinase-2 (MMP-2) and MMP-9. Besides, the β-catenin inhibitor XAV939 blocked the enhanced cell growth, migration, and invasion caused by ARHGAP30 knockdown. Thus, the Wnt/β-catenin pathway mediated the functions of ARHGAP30 in lung cancer cells.
ARHGAP30 acts as a tumor suppressor in lung cancer by suppressing Wnt/β-catenin signaling.
Rho GTP酶激活蛋白30（ARHGAP30）是Rho GTP酶激活蛋白（Rho GAPs）家族的成员之一，在细胞骨架组织和细胞黏附的调节中发挥重要作用。
分别通过定量实时PCR和蛋白质免疫印迹法评估mRNA和蛋白表达。采用细胞计数试剂盒-8（CCK-8）和Transwell实验检测细胞增殖、迁移和侵袭能力。
与非癌标本和正常支气管上皮细胞系相比，肺癌标本和细胞系中ARHGAP30表达分别下调。此外，体外实验表明，ARHGAP30过表达抑制肺癌细胞的增殖、迁移和侵袭能力。此外，利用癌症基因组图谱（TCGA）肺癌数据集进行的生物信息学分析显示，ARHGAP30表达与Wnt信号通路呈负相关。ARHGAP30的强制表达降低了β-连环蛋白、c-Myc、基质金属蛋白酶-2（MMP-2）和MMP-9的mRNA和蛋白水平。此外，β-连环蛋白抑制剂XAV939可阻断由ARHGAP30敲低引起的细胞生长、迁移和侵袭增强。因此，Wnt/β-连环蛋白通路介导了ARHGAP30在肺癌细胞中的功能。
ARHGAP30通过抑制Wnt/β-连环蛋白信号传导在肺癌中发挥肿瘤抑制作用。
