Department of Urology, Jena University Hospital, 07740 Jena, Germany.
RNA Bioinformatics and High-Throughput Analysis, Friedrich Schiller University Jena, 07743 Jena, Germany.
Cells. 2021 Jan 6;10(1):80. doi: 10.3390/cells10010080.
Bladder cancer is a very heterogeneous disease and the molecular mechanisms of carcinogenesis and progression are insufficiently investigated. From the DNA sequencing analysis of matched non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) samples from eight patients, we identified the tumour-associated gene SLC35F2 to be mutated in the 5' and 3' untranslated region (UTR). One mutation in 3'UTR increased the luciferase activity reporter, suggesting its influence on the protein expression of SLC35F2. The mRNA level of SLC35F2 was increased in MIBC compared with NMIBC. Furthermore, in immunohistochemical staining, we observed a strong intensity of SLC35F2 in single tumour cells and in the border cells of solid tumour areas with an atypical accumulation around the nucleus, especially in the MIBC. This suggests that SLC35F2 might be highly expressed in aggressive and invasive tumour cells. Moreover, knockdown of SLC35F2 repressed the growth of bladder cancer cells in the monolayer and spheroid model and suppressed migration and invasion of bladder cancer cells. In conclusion, we suggest that SLC35F2 is involved in bladder cancer progression and might provide a new therapeutic approach, for example, by the anti-cancer drug YM155, a cargo of the SLC35F2 transporter.
膀胱癌是一种非常异质性的疾病，其致癌和进展的分子机制尚未得到充分研究。我们对 8 名患者的非肌肉浸润性膀胱癌（NMIBC）和肌肉浸润性膀胱癌（MIBC）样本进行 DNA 测序分析，发现肿瘤相关基因 SLC35F2 在 5'和 3'非翻译区（UTR）发生突变。3'UTR 中的一个突变增加了荧光素酶活性报告，提示其对 SLC35F2 蛋白表达的影响。与 NMIBC 相比，SLC35F2 在 MIBC 中的 mRNA 水平增加。此外，在免疫组织化学染色中，我们观察到在单个肿瘤细胞和实体瘤区域边界细胞中 SLC35F2 的强度很强，在核周围有异常堆积，尤其是在 MIBC 中。这表明 SLC35F2 可能在侵袭性和侵袭性肿瘤细胞中高度表达。此外，SLC35F2 的敲低抑制了单层和球体模型中膀胱癌细胞的生长，并抑制了膀胱癌细胞的迁移和侵袭。总之，我们认为 SLC35F2 参与膀胱癌的进展，并且可能提供新的治疗方法，例如，通过 SLC35F2 转运体的抗癌药物 YM155。
