Transcriptional factor III A promotes colorectal cancer progression by upregulating cystatin A.
Transcriptional factor III A promotes colorectal cancer progression by upregulating cystatin A.
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DOI：
10.4251/wjgo.v14.i10.1918
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发表时间：
2022-10-15
影响因子：
3
通讯作者：
Tang FQ
中科院分区：
文献类型：
--
作者：
Wang J;Tan Y;Jia QY;Tang FQ
晚期结直肠癌（CRC）通常预后差，死亡率高。阐明结直肠癌进展的分子机制对于开发新的诊断和治疗策略以改善结直肠癌的预后和降低死亡率是必要的。转录因子III A （GTF3A）是一种RNA聚合酶III转录因子，是肿瘤发生的关键驱动因素，可加剧结直肠癌细胞的生长。验证GTF3A是否通过调节胱抑素A （cystatin A, Csta）基因的表达促进结直肠癌的进展，探讨GTF3A是否可以作为结直肠癌患者的预后生物标志物和治疗靶点。采用免疫组织化学方法检测含有90对结直肠癌组织及邻近非肿瘤组织的人组织微阵列，以及含有20对结直肠癌组织及邻近非肿瘤组织及转移组织的人组织微阵列中GTF3A的表达。分析患者的生存率。设计短发夹Gtf3a和Csta，分别阻断Gtf3a和Csta基因的表达。通过体内肿瘤生长实验来证实GTF3A是否促进CRC细胞的体内增殖。采用电泳迁移量转移法和荧光原位杂交法检测GTF3A与Csta的相互作用，荧光素酶活性法检测GTF3A与Csta基因的表达。采用rna测序（RNA-Seq）和数据分析方法筛选GTF3A靶基因。GTF3A在结直肠癌组织和淋巴结转移组织中的表达高于邻近正常组织。GTF3A与CRC预后相关，GTF3A基因的敲低会在体内和体外损害CRC细胞的增殖、侵袭和运动能力。此外，RNA-Seq分析显示GTF3A可能上调Csta的表达，而荧光素酶活性分析显示GTF3A与Csta基因启动子结合，增加Csta转录。此外，CSTA还能调节上皮-间质转化（EMT）标志物的表达。GTF3A通过结合CSTA启动子增加CSTA表达，CSTA水平升高通过调节EMT促进CRC进展。抑制GTF3A可阻止结直肠癌的进展。因此，GTF3A是CRC潜在的新型治疗靶点和生物标志物。
Advanced colorectal cancer (CRC) generally has poor outcomes and high mortality rates. Clarifying the molecular mechanisms underlying CRC progression is necessary to develop new diagnostic and therapeutic strategies to improve CRC outcome and decrease mortality. Transcriptional factor III A (GTF3A), an RNA polymerase III transcriptional factor, is a critical driver of tumorgenesis and aggravates CRC cell growth. To confirm whether GTF3A promotes CRC progression by regulating the expression of cystatin A (Csta) gene and investigate whether GTF3A can serve as a prognostic biomarker and therapeutic target for patients with CRC. Human tissue microarrays containing 90 pairs of CRC tissues and adjacent non-tumor tissues, and human tissue microarrays containing 20 pairs of CRC tissues, adjacent non-tumor tissues, and metastatic tissues were examined for GTF3A expression using immunohistochemistry. The survival rates of patients were analyzed. Short hairpin GTF3As and CSTAs were designed and packaged into the virus to block the expression of Gtf3a and Csta genes, respectively. In vivo tumor growth assays were performed to confirm whether GTF3A promotes CRC cell proliferation in vivo. Electrophoretic mobility shift assay and fluorescence in situ hybridization assay were used to detect the interaction of GTF3A with Csta, whereas luciferase activity assay was used to evaluate the expression of the Gtf3a and Csta genes. RNA-Sequencing (RNA-Seq) and data analyses were used to screen for target genes of GTF3A. The expression of GTF3A was higher in CRC tissues and lymph node metastatic tissues than in the adjacent normal tissues. GTF3A was associated with CRC prognosis, and knockdown of the Gtf3a gene impaired CRC cell proliferation, invasion, and motility in vitro and in vivo. Moreover, RNA-Seq analysis revealed that GTF3A might upregulate the expression of Csta, whereas the luciferase activity assay showed that GTF3A bound to the promoter of Csta gene and increased Csta transcription. Furthermore, CSTA regulated the expression of epithelial-mesenchymal transition (EMT) markers. GTF3A increases CSTA expression by binding to the Csta promoter, and increased CSTA level promotes CRC progression by regulating the EMT. Inhibition of GTF3A prevents CRC progression. Therefore, GTF3A is a potential novel therapeutic target and biomarker for CRC.
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影响因子：
--
作者：
Lei J;Chen S;Zhong S
通讯作者：
Zhong S
影响因子：
64.5
作者：
BIRKENMEIER, EH;BROWN, DD;JORDAN, E
通讯作者：
JORDAN, E
DOI：
10.1002/ar.23311
发表时间：
2016-04-01
影响因子：
2
作者：
Lin, Yang-Yuan;Chen, Zhi-Wei;Xie, Qun
通讯作者：
Xie, Qun
影响因子：
5
作者：
Choi, Eun Hwa;Kim, Jong-Tae;Lee, Hee Gu
通讯作者：
Lee, Hee Gu
影响因子：
--
作者：
Onofrillo C;Galbiati A;Montanaro L;Derenzini M
通讯作者：
Derenzini M