中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (9): 674-681.doi: 10.19401/j.cnki.1007-3639.2020.09.006

• 论著 • 上一篇    下一篇

FAM83H在食管鳞癌中的表达及对癌细胞生物学行为的影响

冯 博,王高燕,梁晓亮,吴 峥,郭艳丽,沈素朋,郭 炜   

  1. 河北医科大学第四医院肿瘤研究所,河北 石家庄 050011
  • 出版日期:2020-09-30 发布日期:2020-10-12
  • 通信作者: 郭 炜 E-mail: guowei7303@163.com
  • 基金资助:
    国家自然科学基金(81472335,81772612)。

The expression level of FAM83H in esophageal squamous cell carcinoma and its effect on biological characteristics of esophageal cancer cells

FENG Bo, WANG Gaoyan, LIANG Xiaoliang, WU Zheng, GUO Yanli, SHEN Supeng, GUO Wei   

  1. Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
  • Published:2020-09-30 Online:2020-10-12
  • Contact: GUO Wei E-mail: guowei7303@163.com

摘要: 背景与目的:食管鳞癌是常见的消化道恶性肿瘤,基因异常表达参与食管鳞癌的恶性生物学行为。探讨转化生长因子-β1(transforming growth factor-β1,TGF-β1)诱导的FAM83H在食管鳞癌组织中的表达水平,以及其表达水平与临床病理学参数之间的关系,初步研究FAM83H对食管癌细胞生物学行为的影响。方法:用TGF-β1处理食管癌细胞Eca109后,在倒置显微镜下观察Eca109细胞形态学的变化。应用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测TGF-β1处理前后食管癌细胞中上皮-间充质转化(epithelial-mesenchymal transition,EMT)相关标志物以及FAM83H表达水平的变化。应用RTFQ-PCR检测FAM83H在不同食管癌细胞系、67例2015—2017年河北医科大学第四医院生物样本库收集的食管鳞癌组织及癌旁正常组织中的表达情况,并分析其表达水平与临床病理学参数之间的关系。应用MTS实验以及transwell小室迁移、侵袭实验检测FAM83H在体外对食管癌细胞增殖、迁移及侵袭能力的影响。结果:TGF-β1处理后,Eca109细胞的形态变为细长梭形、纺锤形,呈现出明显的间充质细胞形态;Eca109细胞中E-cadherin表达水平降低,而N-cadherin、vimentin、Snail、Twist 1表达水平均显著升高(P<0.05)。同时,TGF-β1处理后,FAM83H表达水平上调(P<0.01)。FAM83H在食管鳞癌组织中表达升高(P<0.05),与食管鳞癌患者病理学分化程度相关(P<0.05)。FAM83H在食管癌细胞系中表达升高(P<0.01)。转染针对FAM83H的小干扰RNA后,可以显著抑制FAM83H的表达水平(P<0.05)。在体外FAM83H促进食管癌细胞的增殖、迁移及侵袭(P<0.05)。结论:TGF-β1诱导EMT过程以及FAM83H表达,FAM83H表达水平升高可能与食管鳞癌的发生、发展相关,且在体外促进食管癌细胞的增殖、迁移及侵袭。

关键词: FAM83H, 食管鳞癌, 生物学行为, 上皮-间充质转化

Abstract: Background and purpose: Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor, in which abnormal gene expression is involved in the malignant biological behavior of ESCC. This study aimed to investigate the expression level of transforming growth factor-β1 (TGF-β1)-induced FAM83H in ESCC and its relationship with clinicopathological characteristics, and to explore the effects of FAM83H on biological behavior of esophageal cancer cells in vitro. Methods: The cell morphology was measured under an inverted microscope in TGF-β1-treated Eca109 cells. The expression levels of epithelial-mesenchymal transition (EMT)-related markers and FAM83H were detected in TGF-β1-treated cells compared with untreated cells by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The expression level of FAM83H in different esophageal cancer cell lines and 67 pairs of ESCC tissues and corresponding normal tissues collected from the biological sample bank of the Fourth Hospital of Hebei Medical University from 2015 to 2017 were detected by RTFQ-PCR, and the associations between FAM83H expression level and clinicopathological characteristics were also analyzed. The effects of FAM83H on proliferation, migration and invasion of esophageal cancer cells were examined by MTS, transwell migration, and invasion assays. Results: The cells underwent morphological changes to a spindle-shaped and slender appearance in TGF-β1-treated cells and showed obvious mesenchymal cell morphology. Besides, Eca109 cells treated with TGF-β1 displayed decreased expression level of E-cadherin, as well as upregulated expression levels of N-cadherin, vimentin, Snail and Twist 1 (P<0.05). Meanwhile, upregulation of FAM83H was detected in TGF-β1-treated cells (P<0.01). The expression level of FAM83H was significantly upregulated in ESCC (P<0.05), and was correlated with pathological differentiation (P<0.05). The expression level of FAM83H was also elevated in esophageal cancer cell lines (P<0.01). FAM83H expression level was also markedly inhibited by transfecting small interfering RNA (P<0.05). FAM83H reinforced esophageal cancer cell proliferation, migration and invasion (P<0.05). Conclusion: TGF-β1 induced EMT and FAM83H expression. The high expression level of FAM83H may be related to the occurrence and development of ESCC, and promoted the proliferation, migration and invasion of esophageal carcinoma cells in vitro.

Key words: FAM83H, Esophageal squamous cell carcinoma, Biological characteristics, Epithelial-mesenchymal transition