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BZW1 通过调节 TGF-β1/Smad 通路促进前列腺癌细胞增殖。

BZW1 promotes cell proliferation in prostate cancer by regulating TGF-β1/Smad pathway.

机构信息

Department of Urology Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.

Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Cell Cycle. 2021 May;20(9):894-902. doi: 10.1080/15384101.2021.1909242. Epub 2021 Apr 22.

Abstract

Recently, basic leucine zipper and the W2 domain-containing protein 1 (BZW1) are reported to be implicated in tumor progression. However, the role of BZW1 in prostate cancer remains unknown. This study is aimed to investigate the expression of BZW1 and its influence on cell proliferation in prostate cancer. Then, the expression levels of BZW1 were measured in 136 cases of prostate cancer and matched adjacent non-cancerous prostate tissues by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The effect of BZW1 on cell proliferation was further explored. QRT-PCR analysis showed that the mRNA levels of BZW1 in prostate cancer were significantly greater compared with those in matched adjacent non-cancerous prostate tissues (< 0.001). IHC results showed that the high-expression rates of BZW1 in prostate cancer and matched adjacent non-cancerous prostate tissues were 68.4% and 32.4%, and the difference was statistically significant (< 0.001). BZW1 high expression significantly correlated with T stage, lymph node metastasis, prostate-specific antigen (PSA) and Gleason score (< 0.05). Patients with BZW1 high expression presented unfavorable prognosis compared with those with BZW1 low expression (= 0.002). In addition, CCK-8 and colony formation assays revealed that BZW1 overexpression significantly promoted cell proliferation . Tumor xenograft has shown that BZW1 knockdown significantly inhibited tumor growth . Moreover, BZW1 overexpression activated the TGF-β1/Smad1/Smad3 pathway. Therefore, these data indicate that BZW1 overexpression predicts poorer prognosis and promotes cell proliferation in prostate cancer by regulating TGF-β1/Smad pathway.

摘要

最近,碱性亮氨酸拉链和 W2 结构域蛋白 1(BZW1)被报道与肿瘤进展有关。然而,BZW1 在前列腺癌中的作用尚不清楚。本研究旨在探讨 BZW1 的表达及其对前列腺癌细胞增殖的影响。然后,通过定量实时聚合酶链反应(qRT-PCR)和免疫组织化学(IHC)检测 136 例前列腺癌和配对的相邻非癌前列腺组织中 BZW1 的表达水平。进一步探讨了 BZW1 对细胞增殖的影响。qRT-PCR 分析显示,前列腺癌中 BZW1 的 mRNA 水平明显高于配对的相邻非癌前列腺组织(<0.001)。免疫组织化学结果显示,前列腺癌和配对的相邻非癌前列腺组织中 BZW1 的高表达率分别为 68.4%和 32.4%,差异有统计学意义(<0.001)。BZW1 高表达与 T 分期、淋巴结转移、前列腺特异性抗原(PSA)和 Gleason 评分显著相关(<0.05)。BZW1 高表达患者的预后不如 BZW1 低表达患者(=0.002)。此外,CCK-8 和集落形成实验表明,BZW1 过表达显著促进细胞增殖。肿瘤异种移植表明,BZW1 敲低显著抑制肿瘤生长。此外,BZW1 过表达激活了 TGF-β1/Smad1/Smad3 通路。因此,这些数据表明,BZW1 过表达预示着前列腺癌预后较差,并通过调节 TGF-β1/Smad 通路促进细胞增殖。

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