Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer.
Targeting PLA2G16, a lipid metabolism gene, by Ginsenoside Compound K to suppress the malignant progression of colorectal cancer.
复制标题
靶向Ginsenoside化合物K靶向PLA2G16，一种脂质代谢基因，以抑制结直肠癌的恶性进展。
DOI：
10.1016/j.jare.2021.06.009
复制
发表时间：
2022-03
影响因子：
10.7
通讯作者：
Tan Z
中科院分区：
文献类型：
--
作者：
Yang L;Zheng L;Xie X;Luo J;Yu J;Zhang L;Meng W;Zhou Y;Chen L;Ouyang D;Zhou H;Tan Z
PLA 2G 16在结直肠癌中表达上调，并且PLA 2G 16的高表达与进展期相关。PLA 2G 16通过Hippo信号通路促进CRC的恶性进展。GCK通过抑制PLA 2G 16的蛋白表达发挥其抗CRC作用。通过靶向PLA 2G 16为CRC治疗的有效治疗策略的开发提供了新的见解。结直肠癌（Colorectal cancer，CRC）是一种常见的恶性肿瘤，全球发病率高，转移率高，治愈率低。脂代谢相关基因的改变可影响结直肠癌的发生和发展，可能成为结直肠癌潜在的治疗靶点。因此，从脂代谢相关基因入手，寻找治疗肿瘤的天然药物可能成为CRC研究的新方向。本研究旨在探讨脂质代谢关键基因PLA 2G 16对大肠癌生物学功能的影响，以及GCK抗大肠癌作用是否与PLA 2G 16有关。为了探讨PLA 2G 16在体内外结直肠癌中的作用，我们进行了细胞增殖、迁移、侵袭和裸鼠成瘤试验。对于其作用机制，我们设计了RNA-seq分析，并通过免疫印迹和免疫荧光实验进行了验证。随后，我们通过免疫印迹和拯救实验发现GCK的抗CRC作用与PLA 2G 16有关。我们发现大肠癌组织中PLA 2G 16的表达明显高于癌旁正常组织，并且PLA 2G 16的高表达与大肠癌患者的不良预后相关。此外，通过RNA-seq分析确定，PLA 2G 16通过抑制Hippo信号通路促进CRC的恶性进展，并且GCK通过抑制PLA 2G 16的蛋白表达在体外和体内发挥抗CRC作用。本研究结果提示PLA 2G 16通过抑制Hippo信号通路促进大肠癌的恶性进展，GCK的抗大肠癌作用是通过抑制PLA 2G 16的蛋白表达。
PLA2G16 is up-regulated in CRC, and high expression of PLA2G16 is associated with the advanced stages. PLA2G16 promotes the malignant progression of CRC through the Hippo signaling pathway. GCK exerts its anti-CRC effects by inhibiting the protein expression of PLA2G16. Provide a new insights towards the development of effective therapeutic strategies for CRC treatment by targeting PLA2G16. Colorectal cancer (CRC) is a common malignant tumor with a high global incidence, metastasis rate and low cure rate. Changes in lipid metabolism-related genes can affect the occurrence and development of CRC, and may be a potential therapeutic target for CRC. Therefore, starting from lipid metabolism-related genes to find natural medicines for tumor treatment may become a new direction in CRC research. This study aimed to investigate the effect of PLA2G16, a key gene involved in lipid metabolism, on the biological function of CRC, and whether the anti-CRC effect of GCK is related to PLA2G16. To explore the role of PLA2G16 in CRC in vitro and in vivo, we performed cell proliferation, migration, invasion and nude mice tumorigenesis assays. As for the mechanism, we designed RNA-seq analysis and verified by western blotting and immunofluorescence experiments. Subsequently, we found the anti-CRC effect of GCK is related to PLA2G16 through western blotting and rescue experiments. We showed that PLA2G16 was significantly higher in CRC tissues than the adjacent normal appearing tissues, and high PLA2G16 expression correlates with unfavorable prognosis of CRC patients. Further, PLA2G16 promoted the malignant progression of CRC by inhibiting the Hippo signaling pathway determined by RNA-seq analysis, and GCK exerted anti-CRC effects by inhibiting the protein expression of PLA2G16 in vitro and in vivo. Our results suggested that PLA2G16 promote the malignant progression of CRC by inhibiting the Hippo signaling pathway and the anti-CRC effect of GCK is through inhibiting the protein expression of PLA2G16.
登录
查看更多内容
影响因子：
9
作者：
Nakanishi, Masako;Rosenberg, Daniel W.
通讯作者：
Rosenberg, Daniel W.
circFNDC3B编码的新型蛋白质通过调节结肠癌中的Snail抑制肿瘤进展和EMT
影响因子：
37.3
作者：
Pan, Zihao;Cai, Jianye;Zhang, Lei
通讯作者：
Zhang, Lei
影响因子：
3.4
作者：
Li, Wei;Zhang, Ming;Yang, Geng-Liang
通讯作者：
Yang, Geng-Liang
影响因子：
120.7
作者：
Kahn, Katherine L.;Adams, John L.;Weeks, Jane C.;Chrischilles, Elizabeth A.;Schrag, Deborah;Ayanian, John Z.;Kiefe, Catarina I.;Ganz, Patricia A.;Bhoopalam, Nirmala;Potosky, Arnold L.;Harrington, David P.;Fletcher, Robert H.
通讯作者：
Fletcher, Robert H.
影响因子：
--
作者：
Lim HK;Bae W;Lee HS;Jung J
通讯作者：
Jung J