Zhang Shenglai, Chu Xiaoqin, Zhang Yan, Qiu Jianwei, Pan Liuhong, Gu Liugen, Kang Haifeng, Wang Lin
Department of Gastroenterology, The Second Affiliated Hospital of Nantong University, Nantong, China.
Department of Gastroenterology, Hai'an People's Hospital, Hai'an, China.
Transl Cancer Res. 2025 Feb 28;14(2):717-730. doi: 10.21037/tcr-24-1933. Epub 2025 Feb 26.
It remains to refresh the understanding about the pathogenic mechanism of esophageal squamous cell carcinoma (ESCC). This study aimed to profile the expression of muscleblind like protein 2 (MBNL2), as well as its associations with ESCC behaviors.
Bioinformatic tools were used to mine The Cancer Genome Atlas (TCGA) database for the expression data of MBNL2 in ESCC. The expression of MBNL2 in tissue microarray of 179 ESCC patients was determined by immunohistochemistry (IHC), and the relationship of MBNL2 with patients' clinical and pathological characteristics was analyzed. The expression of MBNL2 was tested in fresh ESCC and adjacent normal tissues . Experiments about cellular invasion, migration and proliferation were performed to detect the impacts of silencing MBNL2 on the biological behaviors of ESCC, and the positive results were checked .
In the TCGA database, the expression of MBNL2 in ESCC was higher than that in adjacent tissues (P<0.05). The protein level of MBNL2 in the tissue microarray of 179 ESCC patients was positively correlated with tumor stage and lymph node metastasis, and negatively correlated with the prognosis of patients. The expression of MBNL2 was significantly upregulated in five fresh ESCC tissues, compared to that in adjacent tissues. In functional experiments, knocking down MBNL2 significantly inhibited the migration and invasion of ESCC cell lines KYSE150 and Eca109, but had no significant effect on their proliferation. Finally, silencing MBNL2 inhibited the epithelial-mesenchymal transition (EMT) of ESCC cells, as evidenced by the upregulation of E-cadherin, the downregulation of Snail and Slug.
MBNL2 is highly expressed in ESCC and associated with its Tumor Node Metastasis (TNM) stage, lymph node metastasis and prognosis. MBNL2 may promote ESCC progression through facilitating EMT.
有必要更新对食管鳞状细胞癌(ESCC)致病机制的认识。本研究旨在分析肌肉盲样蛋白2(MBNL2)的表达情况及其与ESCC生物学行为的关系。
利用生物信息学工具挖掘癌症基因组图谱(TCGA)数据库中ESCC患者MBNL2的表达数据。采用免疫组织化学(IHC)法检测179例ESCC患者组织芯片中MBNL2的表达,并分析其与患者临床病理特征的关系。检测新鲜ESCC组织及癌旁正常组织中MBNL2的表达。进行细胞侵袭、迁移和增殖实验,检测沉默MBNL2对ESCC生物学行为的影响,并验证阳性结果。
在TCGA数据库中,ESCC中MBNL2的表达高于癌旁组织(P<0.05)。179例ESCC患者组织芯片中MBNL2的蛋白水平与肿瘤分期和淋巴结转移呈正相关,与患者预后呈负相关。与癌旁组织相比,5例新鲜ESCC组织中MBNL2的表达显著上调。在功能实验中,敲低MBNL2可显著抑制ESCC细胞系KYSE150和Eca109的迁移和侵袭,但对其增殖无显著影响。最后,沉默MBNL2可抑制ESCC细胞的上皮-间质转化(EMT),表现为E-钙黏蛋白上调,Snail和Slug下调。
MBNL2在ESCC中高表达,与其肿瘤淋巴结转移(TNM)分期、淋巴结转移及预后相关。MBNL2可能通过促进EMT促进ESCC进展。