Song Jinsoo, Park Sujeong, Oh Jinjoo, Kim Deokha, Ryu Ji Hyun, Park Won Cheol, Baek In-Jeoung, Cheng Xi, Lu Xin, Jin Eun-Jung
Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 54538, Korea.
Integrated Omics Institute, Wonkwang University, Iksan, Chunbuk 54538, Korea.
Cancers (Basel). 2020 Mar 2;12(3):576. doi: 10.3390/cancers12030576.
Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that -driven CRC tumors demonstrate dysfunctional peroxisomal b-oxidation and identified (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In -driven CRC tumors, the expression level of was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into knockout () mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of -overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of and mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in colons. Upregulated levels of β-catenin were observed in the colons of and AOM/DSStreated mice and downstream targets of β-catenin such as , and , were also significantly increased in the colon of mice. We observed an increased level of palmitic acid in the colon of mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of b-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal in -driven CRC development.
研究表明，过氧化物酶体脂质代谢失调可能在结直肠癌（CRC）发展中起重要作用。在此，我们发现由[具体因素]驱动的CRC肿瘤表现出过氧化物酶体β-氧化功能障碍，并鉴定出[基因名称（过氧化物酶体辅酶A二磷酸酶NUDT7）]是相关的过氧化物酶体基因之一。在由[具体因素]驱动的CRC肿瘤中，[基因名称]的表达水平显著降低。将氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）处理敲除[基因名称]的（[基因名称]敲除）小鼠，显著诱导脂质积累和CRC相关基因的表达水平，而将过表达[基因名称]的LS-174T细胞异种移植到小鼠体内则显著降低脂质积累和CRC相关基因的表达水平。对用AOM/DSS处理的[基因名称]敲除和野生型小鼠的结肠进行微阵列的 Ingenuity 通路分析表明，Wnt信号通路是[基因名称]敲除小鼠结肠中激活的信号通路之一。在[基因名称]敲除和AOM/DSS处理的野生型小鼠结肠中观察到β-连环蛋白水平上调，并且在[基因名称]敲除小鼠结肠中，β-连环蛋白的下游靶标如[具体基因名称1]、[具体基因名称2]和[具体基因名称3]也显著增加。我们观察到[基因名称]敲除小鼠结肠中棕榈酸水平升高，并且将棕榈酸共轭壳聚糖贴片附着到小鼠结肠中可诱导β-连环蛋白和CRC相关基因的表达水平。总体而言，我们的数据揭示了过氧化物酶体[基因名称]在由[具体因素]驱动的CRC发展中的新作用。
