Tumor-suppressive role of the musculoaponeurotic fibrosarcoma gene in colorectal cancer
Tumor-suppressive role of the musculoaponeurotic fibrosarcoma gene in colorectal cancer
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DOI：
10.1016/j.isci.2023.106478
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发表时间：
2023-04-04
期刊：
影响因子：
5.8
通讯作者：
Yamamoto，Hirofumi
中科院分区：
文献类型：
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作者：
Itakura，Hiroaki;Hata，Tsuyoshi;Yamamoto，Hirofumi
使用microrna miR-200c、miR-302s和miR-369s对体细胞进行重编程可导致人类结直肠癌（CRC）细胞中细胞周期蛋白依赖性激酶抑制剂的表达增加并抑制肿瘤生长。在这里，我们研究了这些microrna是否抑制结直肠肿瘤的发生；Apcmice，这是容易发生结肠和直肠息肉。重复施用microRNAs抑制息肉的形成。微阵列分析显示，据报道在多发性骨髓瘤和T细胞淋巴瘤中显示癌基因样行为的c-MAF在肿瘤样品中减少，但在microrna处理的正常粘膜中增加。免疫组织化学鉴定c-MAF的下调是CRC的早期肿瘤发生事件，低c-MAF表达与预后不良相关。值得注意的是，c-MAF表达和p53蛋白水平在结直肠癌样本中呈负相关，c-MAF敲除导致偶氮甲烷/葡聚糖硫酸钠处理小鼠的肿瘤形成增强，并激活促癌基因。c-MAF可能在结直肠癌的发展中发挥肿瘤抑制作用。
Somatic cell reprogramming using the microRNAs miR-200c, miR-302s, and miR-369s leads to increased expression of cyclin-dependent kinase inhibitors in human colorectal cancer (CRC) cells and suppressed tumor growth. Here, we investigated whether these microRNAs inhibit colorectal tumorigenesis inCPC;Apcmice, which are prone to colon and rectal polyps. Repeated administration of microRNAs inhibited polyp formation. Microarray analysis indicated that c-MAF, which reportedly shows oncogene-like behavior in multiple myeloma and T cell lymphoma, decreased in tumor samples but increased in microRNA-treated normal mucosa. Immunohistochemistry identified downregulation of c-MAF as an early tumorigenesis event in CRC, with low c-MAF expression associated with poor prognosis. Of note, c-MAF expression and p53 protein levels were inversely correlated in CRC samples.c-MAFknockout led to enhanced tumor formation in azoxymethane/dextran sodium sulfate–treated mice, with activation of cancer-promoting genes. c-MAF may play a tumor-suppressive role in CRC development.