通過綜合生物信息學分析和化合物文庫篩選篩選前列腺癌潛在的抗轉移藥物

2023年5月，中國華南大學衡陽醫學院第二附屬醫院泌尿科;中南大學湘雅第二醫院皮膚科;中南大學湘雅醫院泌尿科;吉首大學**附屬醫院泌尿科;湘雅口腔醫院及醫學院；中南大學口腔外科，中南大學湘雅第二醫院甲狀腺專科普外科 (Department of Urology, The Second Affiliated Hospital, Hengyang Medical School,University of South China, Hengyang, Hunan,China；Department of Dermatology, Second Xiangya；Hospital, Central South University, Changsha,Hunan, China；Department of Urology, Xiangya Hospital,Central South University, Changsha, Hunan,China；Department of Urology, First Affiliated Hospital of Jishou University, Jishou, Hunan,China；Xiangya Stomatological Hospital & School of

Stomatology, Central South University Changsha, Hunan, China；Department of General Surgery Thyroid Specialty, The Second Xiangya Hospital of Central South University, Changsha, Hunan,China) Zhi Wei Li老師研究團隊在《The Journal of Gene Medicine》上發表論文：

“Identifying potential anti-metastasis drugs for prostate cancer through integrative bioinformatics analysis and compound library screening”

“通過綜合生物信息學分析和化合物文庫篩選篩選前列腺癌潛在的抗轉移藥物”

Abstract：

Background: Metastasis poses the greatest threat to the lives of individuals with prostate cancer. Therefore, it is imperative to identify the underlying mechanism driving metastasis. Doing so would facilitate the detection of new diagnostic biomarkers and the advancement of treatment options for patients.

Methods: Metastasis-related modules were identified through weighted gene co-expression network analysis based on microarray GSE6919. Hub genes were confirmed by quantitative real-time PCR across different prostate cell lines and clinic samples. Pivotal genes were determined through integration of RNA and transcription factor-target associated interactions. To predict drugs with potential to suppress tumor metastasis, we applied molecular networks using the DrugBank database. Drug repositioning analysis and confirmation of drug screen were conducted using the compound library. Confirmation of selective cytotoxicity of cupric oxide was carried out via invasion, transwell and apoptosis assays.

Results: We identified five metastasis-related modules. Of these modules, two were identified to represent core dysfunction modules in which five hub genes were determined for each module. Five of these 10 genes correlating with prostate cancer progression. Furthermore, our analysis revealed that there are 36 drugs with the potential to be active against tumor metastasis. Finally, we identified four compounds that have not previously been reported to have any association with cancer therapy. Of these, cupric oxide was determined to have the best chemotherapeutic potential in treating prostate cancer metastasis.

Conclusions: By combining bioinformatics methods with compound library screening, this study proposes a valuable approach to drug discovery. Cupric oxide showed the potential in the treatment of prostate cancer metastasis and deserves further study.

摘要：

背景

轉移對前列腺癌患者的生命構成了**的威脅。因此，明確腫瘤轉移的潛在機制勢在必行。這樣做將有助于檢測新的診斷性生物標志物，并為患者提供治療方案。

方法

通過基于微陣列GSE6919的加權基因共表達網絡分析鑒定轉移相關模塊。Hub基因通過實時熒光定量PCR在不同前列腺細胞系和臨床樣本中得到證實。通過整合RNA和轉錄因子-靶標相關相互作用來確定關鍵基因。為了預測可能抑制腫瘤轉移的藥物，研究人員利用DrugBank數據庫應用分子網絡。利用化合物文庫進行藥物重新定位分析和藥物篩選確認。通過侵襲、transwell和凋亡實驗證實了氧化銅的選擇性細胞毒性。

結果

研究人員確定了5個與轉移相關的模塊。在這些模塊中，確定了兩個代表核心功能障礙模塊，其中每個模塊確定了五個中心基因。這10個基因中有5個與前列腺癌的進展有關。此外，研究人員的分析顯示，有36種藥物具有潛在的抗腫瘤轉移活性。最后，研究人員確定了四種以前沒有報道過的與癌癥治療有任何關聯的化合物。其中，氧化銅被認為在治療前列腺癌轉移方面具有**的化療潛力。

結論

本研究將生物信息學方法與化合物文庫篩選相結合，為藥物發現提供了一條有價值的途徑。氧化銅在前列腺癌轉移治療中具有潛在的應用價值，值得進一步研究。

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