Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
Appl Biochem Biotechnol. 2023 Sep;195(9):5365-5378. doi: 10.1007/s12010-022-03847-2. Epub 2022 Mar 3.
At present times, various kinds of literature have suggested the miR-25 acts as an oncogene in various types of human malignancies and until now, very less work has been performed pertaining to the role of miR-25 in esopharyngeal cancer. This study was performed to confirm that miR-25 is overexpressed in esophageal squamous cell carcinoma (ESCC) tumor tissue as a prognostic biomarker and to clarify the mechanism of miR-25. The expression levels of miR-25 and BTG2 were detected in esophageal squamous cell carcinoma tumor tissue. A stably knocked-down miR-25 cell line (miR-25KD) was established in esophageal squamous cell carcinoma cell lines. Moreover, a CCK-8 assay was performed for determining the role of miR-25 in proliferation. The Transwell assays were organized to detect metastasis. Later, a gene profiling study was carried out to identify the gene expression pertaining to tumor progression. The expression of miR-25 in the esophageal cancer tissues was much higher compared with that in paracarcinoma tissues (6.42±4.28 VS 3.36±2.63, p<0.001). A high level of miR-25 was identified to be correlated with postoperative metastasis (χ=8.187, p =0.004). BTG2 levels were significantly lower in tumor tissues (3.24±2.79) than those in adjacent non-tumor tissues (1.96±1.56 VS 2.64±1.41, p<0.001). Negative signs of BTG2 were also associated with postoperative metastasis (χ=7.766, p=0.005). Besides, BTG2-negative cancer tissues are often accompanied by increased miR-25 expression levels (χ=18.379, p<0.001). Patients with high miR-25 levels were found with worse overall survival (OS) (χ=6.906, p=0.009) and metastasis-free survival (MFS) (χ=4.991, p=0.025). Patients with positive BTG2 had better OS (χ=12.917, p <0.001) and MFS (χ=14.173, p<0.001). Knockdown of miR-25 helped to inhibit the proliferation and metastatic ability of esophageal cancer cells. Also, MiR-25 inhibits the expression of BTG2 directly. Results also show that miR-25 also helps to suppress the expression of vimentin and increase the expressions of E-cadherin and BTG2. MiR-25 promotes ESCC progression by directly inhibiting the expression of BTG2. MiR-25 and BTG2 can be utilized as prognostic biomarkers.
目前，各种文献表明 miR-25 在各种人类恶性肿瘤中作为癌基因发挥作用，直到现在，关于 miR-25 在食管鳞癌中的作用的研究很少。本研究旨在证实 miR-25 在食管鳞状细胞癌（ESCC）肿瘤组织中作为预后生物标志物过表达，并阐明 miR-25 的作用机制。检测了食管鳞状细胞癌肿瘤组织中 miR-25 和 BTG2 的表达水平。在食管鳞状细胞癌细胞系中建立了稳定敲低 miR-25 的细胞系（miR-25KD）。此外，进行 CCK-8 测定以确定 miR-25 在增殖中的作用。进行 Transwell 测定以检测转移。随后，进行了基因谱研究以鉴定与肿瘤进展相关的基因表达。与癌旁组织相比，食管癌组织中 miR-25 的表达明显更高（6.42±4.28 VS 3.36±2.63，p<0.001）。高水平的 miR-25 与术后转移有关（χ=8.187，p=0.004）。肿瘤组织中 BTG2 的水平明显低于相邻非肿瘤组织（3.24±2.79）（2.64±1.41 VS 2.64±1.41，p<0.001）。BTG2 的阴性信号也与术后转移有关（χ=7.766，p=0.005）。此外，BTG2 阴性癌组织常伴有 miR-25 表达水平升高（χ=18.379，p<0.001）。miR-25 水平较高的患者总生存率（OS）（χ=6.906，p=0.009）和无转移生存率（MFS）（χ=4.991，p=0.025）较差。BTG2 阳性患者的 OS（χ=12.917，p<0.001）和 MFS（χ=14.173，p<0.001）较好。敲低 miR-25 有助于抑制食管癌细胞的增殖和转移能力。此外，miR-25 直接抑制 BTG2 的表达。结果还表明，miR-25 还可以帮助抑制波形蛋白的表达并增加 E-钙粘蛋白和 BTG2 的表达。miR-25 通过直接抑制 BTG2 的表达促进 ESCC 进展。miR-25 和 BTG2 可用作预后生物标志物。
