SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2.

SPRY4 suppresses proliferation and induces apoptosis of colorectal cancer cells by repressing oncogene EZH2.
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DOI:
10.18632/aging.202859
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发表时间:
2021-04-20
期刊:
Aging
影响因子:
--
通讯作者:
Yu K
Yu K
中科院分区:
其他
文献类型:
--
作者:
Guo J;Zhu H;Li Q;Dong J;Xiong W;Yu K

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结直肠癌(CRC)是消化道常见的恶性肿瘤,是癌症相关死亡的主要原因。SPRY 4已被报道在多种肿瘤中作为肿瘤抑制基因。本研究旨在评估SPRY 4在结直肠癌(CRC)中的作用并揭示其潜在机制。首先,在CRC细胞系中测量SPRY 4的表达水平。将SPRY 4过表达或沉默质粒转染到CRC细胞中以调节其表达水平。CCK-8、集落形成、EdU测定、伤口愈合和Transwell测定以测定细胞增殖、侵袭和迁移能力。流式细胞术检测细胞凋亡,Western印迹法检测凋亡相关蛋白的表达。接下来,在裸鼠中进行体内肿瘤发生测定。结果表明,SPRY 4在结直肠癌细胞系中的表达低于正常细胞系,SPRY 4过表达可显著抑制SW 480细胞的增殖、迁移和侵袭,促进细胞凋亡。此外,SPRY 4沉默后增强的增殖、侵袭和迁移被EZH 2抑制逆转。此外,我们发现SPRY 4的过表达通过减小肿瘤的大小和重量来抑制体内肿瘤发生。SPRY 4可能是一个潜在的抑癌基因,也可能是影响结直肠癌患者预后的重要因素。
Colorectal cancer (CRC), a common malignant tumor in the digestive tract, is a leading cause of cancer-related death. SPRY4 has been reported to act as a tumor suppressor gene in various tumors. This study aims to assess the role of SPRY4 in colorectal cancer (CRC) and uncover its underlying mechanisms. Firstly, the expression levels of SPRY4 were measured in CRC cell lines. SPRY4-overexpressing or silencing plasmids were transfected into CRC cells to regulate its expression level. CCK-8, colony formation, EdU assay, wound-healing and Transwell assays were performed to determine cell proliferation, invasion and migration abilities. Then, apoptosis was measured by flow cytometry analysis, and the expression of apoptosis-related protein was analyzed by western-blotting. Next, the in vivo tumorigenesis assay was performed in nude mice. According to the results, there was a lower expression of SPRY4 in CRC cell lines compared with normal cell line, and the overexpression of SPRY4 significantly suppressed cell proliferation, migration and invasion, and promoted apoptosis in SW480 cells. Moreover, the enhanced proliferation, invasion and migration upon SPRY4 silencing was reversed by EZH2 inhibition. In addition, we found that the overexpression of SPRY4 inhibited tumorigenesis in vivo by diminishing the size and weight of the tumors. Our study indicates that SPRY4 might be a potential tumor suppressor gene and prognostic factor for patients with CRC.
EZH2的表达与结直肠癌的结果不佳有关。
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