Insulin‐like growth factor‐2 messenger RNA‐binding protein 3 (IGF2BP3) has been reported to contribute to tumorigenesis in several human cancers. However, the biological functions of IGF2BP3 in bladder cancer are poorly understood. We investigated the relation between IGF2BP3 expression and prognosis of bladder cancer patients. Cell proliferation, cell cycle and cell apoptosis assays were performed to assess IGF2BP3 functions. The results showed that IGF2BP3 was overexpressed in bladder cancer tissues compared with that in normal bladder tissues, and its higher expression was closely correlated with poor prognosis in bladder cancer patients. Overexpression of IGF2BP3 markedly promoted cell proliferation and cell cycle progression and inhibited cell apoptosis, while knockdown of IGF2BP3 notably suppressed the proliferation, promoted cell apoptosis and induced cell cycle arrest at the G0/G1 phase. Mechanistically, we revealed that IGF2BP3 promotes the activation of the JAK/STAT pathway in bladder cancer cells. Moreover, the JAK/STAT inhibitor dramatically blocked the tumour‐promoting activity of IGF2BP3. Tumour growth in vivo was also suppressed by knocking down of IGF2BP3. Hence, IGF2BP3 facilitated bladder cancer cell proliferation by activating the JAK/STAT signalling pathway. These findings suggest that IGF2BP3 exhibits an oncogenic effect in human bladder cancer progression.

中文翻译：

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IGF2BP3通过调节人膀胱癌中的JAK/STAT信号通路促进细胞增殖和肿瘤发生

据报道，胰岛素样生长因子-2 信使 RNA 结合蛋白 3 (IGF2BP3) 有助于几种人类癌症的肿瘤发生。然而，人们对IGF2BP3在膀胱癌中的生物学功能知之甚少。我们研究了 IGF2BP3 表达与膀胱癌患者预后之间的关系。进行细胞增殖、细胞周期和细胞凋亡测定以评估IGF2BP3功能。结果显示，与正常膀胱组织相比，IGF2BP3在膀胱癌组织中呈高表达，其高表达与膀胱癌患者预后不良密切相关。IGF2BP3 的过表达显着促进细胞增殖和细胞周期进程并抑制细胞凋亡，而 IGF2BP3 的敲低显着抑制增殖，促进细胞凋亡并诱导细胞周期停滞在 G0/G1 期。从机制上讲，我们揭示了 IGF2BP3 促进膀胱癌细胞中 JAK/STAT 通路的激活。此外，JAK/STAT 抑制剂显着阻断了 IGF2BP3 的促肿瘤活性。通过敲除 IGF2BP3 也抑制了体内肿瘤的生长。因此，IGF2BP3 通过激活 JAK/STAT 信号通路促进膀胱癌细胞增殖。这些发现表明 IGF2BP3 在人类膀胱癌进展中表现出致癌作用。通过敲除 IGF2BP3 也抑制了体内肿瘤的生长。因此，IGF2BP3 通过激活 JAK/STAT 信号通路促进膀胱癌细胞增殖。这些发现表明 IGF2BP3 在人类膀胱癌进展中表现出致癌作用。通过敲除 IGF2BP3 也抑制了体内肿瘤的生长。因此，IGF2BP3 通过激活 JAK/STAT 信号通路促进膀胱癌细胞增殖。这些发现表明 IGF2BP3 在人类膀胱癌进展中表现出致癌作用。