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GALNT12通过加速YAP1核定位促进纤维肉瘤生长。

GALNT12 promotes fibrosarcoma growth by accelerating YAP1 nuclear localization.

作者信息

Yu Site, Feng Wenjie, Zeng Jizhang, Zhou Situo, Peng Yinghua, Zhang Pihong

机构信息

Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Oncol Lett. 2023 Nov 3;26(6):543. doi: 10.3892/ol.2023.14131. eCollection 2023 Dec.

Abstract

Fibrosarcoma is a highly malignant type of soft tissue sarcoma that currently lacks effective treatment options. Polypeptide N-acetylgalactosaminyltransferase 12 (GALNT12) belongs to the uridine diphosphate N-acetylgalactosamine gene family, which is involved in numerous biological processes of diseases, such as tumor progression. Its upregulated expression is closely associated with the development of colorectal cancer. However, research on the role of GALNT12 in fibrosarcoma is currently limited. The present study aimed to assess the expression and biological function of GALNT12 in fibrosarcoma. Patient data and tissue samples were collected and public datasets were obtained from the Gene Expression Omnibus (GSE24369 and GSE21124). Immunofluorescence assays were performed to observe the cellular localization of GALNT12. GALNT12 expression was measured using reverse transcription-quantitative PCR, western blotting and immunohistochemistry. Small interfering RNAs were constructed to knock down GALNT12 expression in HT-1080 cells. Cell Counting Kit-8 and EdU assays were used to assess fibrosarcoma cell proliferation. Wound healing and Transwell assays were used to detect migration. Gene set enrichment analysis was performed to identify key pathways. Paired and unpaired Student's t-test, Fisher's exact test and one-way ANOVA (followed by Tukey's Honest Significant Difference test) were used to analyze the data. It was demonstrated that GALNT12 expression was upregulated in both fibrosarcoma cell lines and tissue samples and predicted poor patient prognosis. experiments demonstrated that high GALNT12 expression levels significantly increased HT-1080 cell proliferation and migration. Furthermore, it was demonstrated that high GALNT12 expression levels were closely associated with the yes1 associated transcriptional regulator (YAP1) signaling pathway. Knockdown of GALNT12 inhibited YAP1 nuclear translocation, which affected activation of key downstream genes including AMOTL2, BIRC5 and CYR61. Therefore, the present study demonstrated that GALNT12 promoted fibrosarcoma progression. GALNT12 could be a potential biomarker for this disease and may potentially provide new ideas for targeted therapy of fibrosarcoma in the future.

摘要

纤维肉瘤是一种高度恶性的软组织肉瘤,目前缺乏有效的治疗方案。多肽N - 乙酰半乳糖胺基转移酶12(GALNT12)属于尿苷二磷酸N - 乙酰半乳糖胺基因家族,其参与多种疾病的生物学过程,如肿瘤进展。其表达上调与结直肠癌的发生发展密切相关。然而,目前关于GALNT12在纤维肉瘤中作用的研究有限。本研究旨在评估GALNT12在纤维肉瘤中的表达及生物学功能。收集患者数据和组织样本,并从基因表达综合数据库(GSE24369和GSE21124)获取公共数据集。进行免疫荧光分析以观察GALNT12的细胞定位。使用逆转录定量PCR、蛋白质印迹法和免疫组织化学检测GALNT12的表达。构建小干扰RNA以敲低HT - 1080细胞中GALNT12的表达。使用细胞计数试剂盒 - 8和EdU分析评估纤维肉瘤细胞增殖。采用伤口愈合实验和Transwell实验检测细胞迁移。进行基因集富集分析以确定关键通路。使用配对和非配对学生t检验、Fisher精确检验和单因素方差分析(随后进行Tukey真实显著性差异检验)分析数据。结果表明,GALNT12在纤维肉瘤细胞系和组织样本中均表达上调,并预示患者预后不良。实验表明,高GALNT12表达水平显著增加HT - 1080细胞的增殖和迁移。此外,结果表明高GALNT12表达水平与Yes1相关转录调节因子(YAP1)信号通路密切相关。敲低GALNT12可抑制YAP1核转位,从而影响包括AMOTL2、BIRC5和CYR61在内的关键下游基因的激活。因此,本研究表明GALNT12促进纤维肉瘤进展。GALNT12可能是该疾病的潜在生物标志物,并可能为未来纤维肉瘤的靶向治疗提供新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8866/10660188/6fb930d94e93/ol-26-06-14131-g00.jpg

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