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FAM107A 作为食管鳞癌的肿瘤抑制因子,抑制其生长和转移。

FAM107A as a tumor suppressor in esophageal squamous carcinoma inhibits growth and metastasis.

机构信息

Department of Thoracic Surgery, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China.

出版信息

Pathol Res Pract. 2023 Dec;252:154945. doi: 10.1016/j.prp.2023.154945. Epub 2023 Nov 11.

Abstract

BACKGROUND

Sequence similarity Family 107 member A (FAM107A) has been recognized as a tumor suppressor of various malignancies, which suppresses tumor proliferation and metastasis. Its specific role in esophageal squamous cell carcinoma (ESCC) remains unclear.

METHODS

Public datasets including Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO), quantitative real-time PCR (qRT-PCR), and Western blot were utilized for comparative analysis of FAM107A expression between ESCC and normal tissues. The link between FAM107A and clinicopathological features, as well as prognosis determined through χ2-test, log-rank analysis, and univariate and multivariate analyses, respectively. The impact of FAM107A on ESCC cell malignant behavior was confirmed through in vitro assays, including cell counting using the Cell Counting Kit-8 (CCK-8), clonal formation, wound healing, and transwell assays. Western blot analysis was employed to assess the effects of FAM107A on tumor epithelial-mesenchymal transition (EMT) and cell cycle-related proteins. Finally, xenograft tumors were developed to investigate the influence of FAM107A on ESCC growth in vivo.

RESULTS

FAM107A exhibited low expression in ESCC tissues. Reduced FAM107A expression was associated with a poorer prognosis and unfavorable clinicopathological characteristics, such as degree of differentiation, T-stage, and N-stage. Overexpression of FAM107A suppressed ESCC cell proliferation, invasion, migration, the EMT process, and cell cycle progression. Finally, FAM107A overexpression inhibited tumor development in vivo.

CONCLUSION

The decreased expression of FAM107A is indicative of a worse prognosis for ESCC patients. FAM107A exerts inhibitory impacts on malignant behavior and may hold promise as a therapeutic target for ESCC.

摘要

背景

序列相似家族 107 成员 A(FAM107A)已被确认为多种恶性肿瘤的肿瘤抑制因子,其可抑制肿瘤增殖和转移。其在食管鳞状细胞癌(ESCC)中的具体作用尚不清楚。

方法

利用公共数据集(包括基因表达谱交互分析(GEPIA)和基因表达综合数据库(GEO))、定量实时 PCR(qRT-PCR)和 Western blot 比较 ESCC 和正常组织中 FAM107A 的表达。通过 χ2 检验、对数秩分析以及单因素和多因素分析分别比较 FAM107A 与临床病理特征和预后的关系。通过体外实验(包括细胞计数试剂盒-8(CCK-8)检测细胞增殖、克隆形成、划痕愈合和 Transwell 实验)证实 FAM107A 对 ESCC 细胞恶性行为的影响。Western blot 分析用于评估 FAM107A 对肿瘤上皮-间充质转化(EMT)和细胞周期相关蛋白的影响。最后,建立异种移植瘤模型以研究 FAM107A 对 ESCC 体内生长的影响。

结果

FAM107A 在 ESCC 组织中表达水平较低。FAM107A 低表达与较差的预后和不良的临床病理特征相关,如分化程度、T 分期和 N 分期。过表达 FAM107A 抑制 ESCC 细胞增殖、侵袭、迁移、EMT 过程和细胞周期进程。最后,FAM107A 过表达抑制了体内肿瘤的发展。

结论

FAM107A 表达降低提示 ESCC 患者预后不良。FAM107A 对恶性行为具有抑制作用,可能成为 ESCC 的治疗靶点。

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