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transcriptional factorⅢA promotes colorectal cancer progression by upregulating cystatin A

World Journal of Gastrointestinal Oncology 2022年第10期14卷 1918-1932页

作者： Jing Wang Yuan Tan Qun-Ying Jia Fa-Qin Tang Hunan Key Laboratory of Oncotarget Gene Hunan Cancer Hospital&The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013Hunan ProvinceChina

BACKGROUND 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 *** 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 *** Human tissue microarrays containing 90 pairs of CRC tissues and adjacent nontumor 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 *** 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, RNASeq 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 increas

关键词： transcription factor iiia Cystatin A Colorectal cancer Epithelial-mesenchymal transition

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