SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7
SLC12A5 interacts and enhances SOX18 activity to promote bladder urothelial carcinoma progression via upregulating MMP7
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SLC12A5 相互作用并增强 SOX18 活性，通过上调 MMP7 促进膀胱尿路上皮癌进展
DOI：
10.1111/cas.14502
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发表时间：
2020-06-13
期刊：
影响因子：
5.7
通讯作者：
Liu, Jianye
中科院分区：
文献类型：
--
作者：
Wang, Long;Zhang, Qun;Liu, Jianye
溶质载体家族 12 成员 5 (SLC12A5) 在膀胱尿路上皮癌中具有致癌作用。本研究旨在探讨SLC12A5在膀胱尿路上皮癌发病机制中的分子机制。功能分析发现，在膀胱尿路上皮癌中，SLC12A5 与 SOX18 相互作用并稳定 SOX18，然后上调基质金属蛋白酶 7 (MMP7)。进行体内和体外测定以确认 SLC12A5 与 SOX18 相互作用对 MMP7 介导的膀胱尿路上皮癌进展的影响。 SLC12A5 在人类膀胱肿瘤中表达上调，并与膀胱尿路上皮癌肿瘤侵袭和转移患者的较差生存率相关，SLC12A5 过表达会促进这种情况。我们证明SLC12A5与SOX18相互作用，然后上调MMP7，从而促进肿瘤进展。重要的是，膀胱尿路上皮癌中SLC12A5的表达与SOX18和MMP7的表达呈正相关。此外，SLC12A5 表达被 miR-133a-3p 抑制。 SLC12A5 的异位表达部分消除了 miR-133a-3p 介导的细胞迁移抑制。 SLC12A5-SOX18 复合物介导的 MMP7 上调在膀胱尿路上皮癌进展中很重要。 miR-133a-3p/SLC12A5/SOX18/MMP7信号轴对于进展至关重要，并提供了针对膀胱尿路上皮癌的有效治疗方法。
Solute carrier family 12 member 5 (SLC12A5) has an oncogenic role in bladder urothelial carcinoma. The present study aimed to characterize the molecular mechanisms of SLC12A5 in bladder urothelial carcinoma pathogenesis. Functional assays identified that in bladder urothelial carcinoma SLC12A5 interacts with and stabilizes SOX18, and then upregulates matrix metalloproteinase 7 (MMP7). In vivo and in vitro assays were performed to confirm the effect of SLC12A5's interaction with SOX18 on MMP7-mediated bladder urothelial carcinoma progression. SLC12A5 was upregulated in human bladder tumors, and correlated with the poor survival of patients with bladder urothelial carcinoma tumor invasion and metastasis, promoted by SLC12A5 overexpression. We demonstrated that SLC12A5 interacted with SOX18, and then upregulated MMP7, thus enhancing tumor progression. Importantly, SLC12A5 expression correlated positively with SOX18 and MMP7 expression in bladder urothelial carcinoma. Furthermore, SLC12A5 expression was suppressed by miR-133a-3p. Ectopic expression of SLC12A5 partly abolished miR-133a-3p-mediated suppression of cell migration. SLC12A5-SOX18 complex-mediated upregulation on MMP7 was important in bladder urothelial carcinoma progression. The miR-133a-3p/SLC12A5/SOX18/MMP7 signaling axis was critical for progression, and provided an effective therapeutic approach against bladder urothelial carcinoma.