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长链非编码RNA FAM87A与胃癌患者的总生存期相关,并促进胃癌细胞的迁移和侵袭。

Long non-coding RNA FAM87A is associated with overall survival and promotes cell migration and invasion in gastric cancer.

作者信息

Jiang Xue, Wu Xiaobin, Lu Manjiao, Fan Wenna, Song Jing, Song Fangzhou

机构信息

Molecular medicine and cancer research center, the basic school of Chongqing Medical University, Chongqing, China.

School of Smart Healthcare Industry, Chongqing City Management College, Chongqing, China.

出版信息

Front Oncol. 2024 Sep 25;14:1448502. doi: 10.3389/fonc.2024.1448502. eCollection 2024.

Abstract

BACKGROUND

The role of long non-coding RNAs (lncRNAs) in the invasion and metastasis of gastric cancer remains largely unclear.

METHODS

Integrating transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, differentially expressed genes were identified in gastric cancer. Using the Catalogue of Somatic Mutations in Cancer (COSMIC) database-curated gene set, lncRNAs associated with invasion and metastasis were identified. The Cox analyses were performed to identify prognostic lncRNAs. The competing endogenous RNA (ceRNA) regulation network was constructed to identify hub lncRNAs in gastric cancer. Functional and pathway analyses were used to investigate the function of identified lncRNAs. RT-qPCR and Transwell assays were used to investigate the expression in gastric cancer tissues and functions in gastric cancer cell lines.

RESULTS

Based on GEO and TCGA databases, 111 differentially expressed lncRNAs were identified between gastric cancer and normal samples. A total of 43 lncRNAs were significantly correlated with hallmark genes of cancer invasion and metastasis. Among them, as a hub lncRNA in the invasion-related ceRNA regulation network, FAM87A showed potential regulation on MAPK signaling and transforming growth factor (TGF) signaling cascade, such as TGFB2, TGFBR1, and TGFBR2. Furthermore, FAM87A also showed a significant correlation with cell adhesion molecules, such as Integrin alpha 6 (ITGA6) and Contactin-1 (CNTN1). RT-qPCR experiments showed that FAM87A expression was upregulated in gastric cancer tissues compared to normal samples (n = 30). Transwell assays showed that FAM87A knockdown inhibited the migration and invasion abilities of gastric cancer cells . Notably, clinical data analysis showed that lncRNA FAM87A could be an independent factor for the overall survival of patients with gastric cancer.

CONCLUSION

LncRNA FAM87A may play a pivotal role in regulating migration and invasion of gastric cancer cells. FAM87A could be a potential biomarker for the overall survival of patients with gastric cancer.

摘要

背景

长链非编码RNA(lncRNA)在胃癌侵袭和转移中的作用仍不清楚。

方法

整合来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的转录组数据,在胃癌中鉴定差异表达基因。使用癌症体细胞突变目录(COSMIC)数据库整理的基因集,鉴定与侵袭和转移相关的lncRNA。进行Cox分析以鉴定预后lncRNA。构建竞争性内源RNA(ceRNA)调控网络以鉴定胃癌中的关键lncRNA。使用功能和通路分析来研究鉴定出的lncRNA的功能。采用RT-qPCR和Transwell实验来研究lncRNA在胃癌组织中的表达及在胃癌细胞系中的功能。

结果

基于GEO和TCGA数据库,在胃癌和正常样本之间鉴定出111个差异表达的lncRNA。共有43个lncRNA与癌症侵袭和转移的标志性基因显著相关。其中,作为侵袭相关ceRNA调控网络中的关键lncRNA,FAM87A对丝裂原活化蛋白激酶(MAPK)信号通路和转化生长因子(TGF)信号级联反应(如TGFB2、TGFBR1和TGFBR2)具有潜在调控作用。此外,FAM87A还与细胞黏附分子(如整合素α6(ITGA6)和接触蛋白-1(CNTN1))显著相关。RT-qPCR实验表明,与正常样本(n = 30)相比,FAM87A在胃癌组织中的表达上调。Transwell实验表明,敲低FAM87A可抑制胃癌细胞的迁移和侵袭能力。值得注意的是,临床数据分析表明lncRNA FAM87A可能是胃癌患者总生存的独立因素。

结论

lncRNA FAM87A可能在调节胃癌细胞迁移和侵袭中起关键作用。FAM87A可能是胃癌患者总生存的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c44/11461168/33c10455452f/fonc-14-1448502-g001.jpg

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