Transcription Factors BARX1 and DLX4 Contribute to Progression of Clear Cell Renal Cell Carcinoma via Promoting Proliferation and Epithelial-Mesenchymal Transition.
Transcription Factors BARX1 and DLX4 Contribute to Progression of Clear Cell Renal Cell Carcinoma via Promoting Proliferation and Epithelial-Mesenchymal Transition.
复制标题
转录因子 BARX1 和 DLX4 通过促进增殖和上皮-间质转化促进透明细胞肾细胞癌的进展
DOI：
10.3389/fmolb.2021.626328
复制
发表时间：
2021
影响因子：
5
通讯作者：
Ye Z
中科院分区：
文献类型：
--
作者：
Sun G;Ge Y;Zhang Y;Yan L;Wu X;Ouyang W;Wang Z;Ding B;Zhang Y;Long G;Liu M;Shi R;Zhou H;Chen Z;Ye Z
转录因子的失调会导致癌症的发生和进展。然而，它们在透明细胞肾细胞癌中的作用仍然很大程度上未知。本研究旨在评估 TF 的临床意义并研究其在 ccRCC 中的潜在分子机制。数据取自癌症基因组图谱肾透明细胞癌队列。采用生物信息学算法进行拷贝数改变突变、差异表达TF分析。进行单变量和多变量 Cox 回归分析，以确定具有临床意义的 TF 并构建六 TF 预后面板。 TF 的表达已在人体组织中得到验证。利用基因集富集分析 (GSEA) 来寻找富集的癌症标志通路。通过功能实验验证 BARX 同源盒 1 (BARX1) 和远端同源盒 4 (DLX4) 在 ccRCC 中的促癌作用，并通过 Western blot 探索其下游通路。结果显示，在转录因子基因中发现了许多CNA和突变。 TF 在 ccRCC 中差异表达。构建了适用的六TF基因预测面板来预测ccRCC患者的总生存率，并通过曲线下面积（AUC）评估其诊断效率。 BARX1和DLX4与不良预后相关，并且它们可以促进ccRCC的增殖和迁移。总之，六-TF 组合可用作 ccRCC 患者的预后生物标志物。 BARX1 和 DLX4 通过促进增殖和上皮间质转化在 ccRCC 中发挥致癌作用。它们有可能成为 ccRCC 的新治疗靶点。
Dysregulation of transcription factors contributes to the carcinogenesis and progression of cancers. However, their roles in clear cell renal cell carcinoma remain largely unknown. This study aimed to evaluate the clinical significance of TFs and investigate their potential molecular mechanisms in ccRCC. Data were accessed from the cancer genome atlas kidney clear cell carcinoma cohort. Bioinformatics algorithm was used in copy number alterations mutations, and differentially expressed TFs’ analysis. Univariate and multivariate Cox regression analyses were performed to identify clinically significant TFs and construct a six-TF prognostic panel. TFs’ expression was validated in human tissues. Gene set enrichment analysis (GSEA) was utilized to find enriched cancer hallmark pathways. Functional experiments were conducted to verify the cancer-promoting effect of BARX homeobox 1 (BARX1) and distal-less homeobox 4 (DLX4) in ccRCC, and Western blot was performed to explore their downstream pathways. As for results, many CNAs and mutations were identified in transcription factor genes. TFs were differentially expressed in ccRCC. An applicable predictive panel of six-TF genes was constructed to predict the overall survival for ccRCC patients, and its diagnostic efficiency was evaluated by the area under the curve (AUC). BARX1 and DLX4 were associated with poor prognosis, and they could promote the proliferation and migration of ccRCC. In conclusion, the six-TF panel can be used as a prognostic biomarker for ccRCC patients. BARX1 and DLX4 play oncogenic roles in ccRCC via promoting proliferation and epithelial–mesenchymal transition. They have the potential to be novel therapeutic targets for ccRCC.