The Journal of Practical Medicine ›› 2024, Vol. 40 ›› Issue (23): 3394-3404.doi: 10.3969/j.issn.1006-5725.2024.23.019
• Reviews • Previous Articles
Ping JIANG1,Xiaoqin LUO2,Shaoqian ZHAI1,Chengzhu CAO1,Zhanhai. SU1()
Received:
2024-09-27
Online:
2024-12-10
Published:
2024-12-16
Contact:
Zhanhai. SU
E-mail:suzhanhai@qhu.edu.cn
CLC Number:
Ping JIANG,Xiaoqin LUO,Shaoqian ZHAI,Chengzhu CAO,Zhanhai. SU. Advances in the role and mechanism of ISG15 in malignant tumours of the gastrointestinal tract[J]. The Journal of Practical Medicine, 2024, 40(23): 3394-3404.
Tab.1
Mechanisms associated with ISG15 in digestive tract cancer"
癌症类型 | 发病机制 | 实验/分析 | ISG15对肿瘤的作用 | 参考 文献 |
---|---|---|---|---|
食管癌 | ISG15是食管癌细胞自噬和化疗敏感性的负向调节器。 | OE19、OE21、OE33、KYSE450、FLO-1细胞系 | 抑制 | |
5-FU诱导的ISG15K表达上调参与调节食管癌细胞对化疗和IFN治疗。 | T.T、TE?2、TE?6细胞系 | - | ||
ISG化促进GRAIL1依赖性CD3降解,抑制T细胞活性 。 | OE19、OE21、OE33、KYSE450、FLO-1细胞系和人体组织 | 促进 | ||
ISG15的上调在放疗诱导的PD-L1阳性肿瘤微环境中可能促进免疫激活,凸显其作为免疫治疗靶点的潜力。 | 人体组织 | 抑制 | ||
作为p53的靶基因,ISG15的mRNA水平可被p53 上调。 | 人体组织 | 促进 | ||
ISG15通过c-MET/Fyn/β- catenin信号通路促进食管鳞状细胞癌的发展。 | YES2、KYSE、COLO680N细胞系和BALB/c裸鼠 | 促进 | ||
胃癌 | ISG15是肠型胃癌关键核心基因。 | 人体组织 | - | |
Linc00673可通过抑制ISG15表达负向调控胃癌细胞的增殖和侵袭能力。 | BGC823、HGC-27、SGC7901细胞系和人体组织 | 促进 | ||
ISG15在胃癌中高表达与CD3表达水平及患者总生存期(OS)缩短相关联。 | 人体组织 | - | ||
ISG化增强CPT诱导的DNA损伤积累,促进细胞凋亡,显著提高胃癌细胞对伊立替康的敏感性。 | 免疫缺陷小鼠和人体组织 | 抑制 | ||
肝癌 | ISG化修饰促进肝细胞癌的增殖和迁移,其高表达与肿瘤的不良预后相关,且不受HBV感染状态影响。 | PLC/PRF/5细胞系 | 促进 | |
18β-甘草次酸激活JAK-STAT信号通路,诱导ISG15等IFN-刺激基因的表达,协同奥沙利铂抑制肝癌进展,增强肿瘤免疫应答。 | RAW246.7、BMDM、BMDC细胞系和C57BL/6雄性小鼠 | 抑制 | ||
ISG15在肝癌组织中高表达,与患者预后不良相关,尤其在病毒性肝炎和饮酒相关肝癌中。 | 人体组织 | 促进 | ||
USP18通过去除ISG15的共价修饰抑制I型干扰素信号通路,促进HBV复制并参与肝癌发展,其表达下调可显著降低HBV DNA水平。 | HepG2、HepG2.2.15、Hep3B、Huh-7、SMMC-7721细胞系 | 抑制 | ||
ISG化干扰XIAP与Survivin的相互作用,稳定Survivin蛋白,从而促进肝细胞癌的增殖和转移。 | Huh7、HepG2、97L细胞系和BALB/c裸鼠以及人体组织 | 促进 | ||
NFE2L3通过调节ISG化p53的蛋白酶体依赖性降解来驱动肝癌细胞增殖。 | HepG2、MHCC97H细胞系BALB/c裸鼠以及人体组织 | 促进 | ||
原发性肝癌中ISG15高表达组较低表达组有更短的OS、PFS及更差的预后。 | 人体组织 | 促进 | ||
ISG化过程涉及的酶(如EFP、HERC5、UBA1和USP18)在肝癌组织中显著高表达。 | 人体组织 | - | ||
ISG15过表达促进HepG2细胞凋亡,增强ISGylation/泛素化,抑制肿瘤生长。 | HepG2细胞系 | 抑制 | ||
IFN-2α通过增加 PI3K / Akt 通路中的 p-Akt( Thr308) 上调 ISG15 的表达。 | HepG2细胞系和生信数据库 | 促进 | ||
eEF1A1通过调控ISG化的水平,影响肝癌细胞在阿霉素治疗环境下的化疗敏感性。 | MCC97H、HepG2、HuH7、Hep3B、SMCC7721细胞系 | 促进 | ||
HZ-6d通过靶向降低HERC5的表达,抑制了p53蛋白依赖于ISG化途径的降解,激活p53抗肿瘤信号通路。 | HepG2、SMCC7721细胞系和BALB/c裸鼠以及人体组织 | 促进 | ||
胰腺癌 | BAG3正向调控ISG15的表达,BAG3敲低通过Ago2对ISG15的翻译水平进行调控从而抑制胰腺导管腺癌干细胞样表型。 | BxPC3、SW1990、PANC-1细胞系和BALB/c裸鼠以及人体组织 | 促进 | |
TRIM29表达下调通过促进ISG15蛋白降解来抑制PDAC干细胞样表型,且游离型ISG15可能作为肿瘤干细胞的支持因子发挥促癌作用。 | BxPC3、SW1990细胞系和BALB/c裸鼠以及人体组织 | 促进 | ||
miR-423-3p靶向下调胰腺癌中ISG15进而降低PD-L1的表达,抑制了胰腺癌细胞的增殖和侵袭性转移。 | BxPC-3、PANC-1、293T细胞系和BALB/c裸鼠以及人体组织 | 抑制 | ||
SMAD4 下调通过抑制Ⅰ型IFN信号通路促进胰腺癌转移。 | PANC-1细胞系和生信数据库 | 抑制 | ||
泛素/ISG15结合酶E2L6(UBE2L6)作为一种ISG15结合酶,在胰腺癌中可能通过促进ISG化,增强了癌细胞的增殖、迁移和侵袭能力 | BxPC-3、PANC-1、AsPC-1、SW1990、MIA PaCa-2细胞系和生信数据库 | 促进 | ||
ISG化调控PaCSCs线粒体健康和代谢可塑性,游离ISG15通过自分泌/旁分泌途径激活细胞干性。 | 异种移植瘤衍生的初级胰腺癌细胞和NU-Foxn1nu裸鼠以及人体组织 | 促进 | ||
ISG15敲除降低了肿瘤程序性死亡配体-1(PDL-1)的表达,增加了 CD8+肿瘤浸润淋巴细胞的数量,抑制胰腺肿瘤的生长。 | Panc02细胞系和C57BL/6小鼠 | 促进 | ||
上调的ISG化增加了吉西他滨耐药性。 | CIPT1、MiaPaCa2、AsPC1、BxPC3、 Capan1、PK1、PK8、PK9、T3M4、KP3细胞系和人体组织 | 促进 | ||
WBSCR22和TRMT112通过负向调控ISG15的转录,协同抑制胰腺癌细胞的增殖、侵袭和成瘤能力。 | PANC-1、BXPC-3、AsPC-1细胞系和BALB/c裸鼠以及生信数据库 | 促进 | ||
ISG15通过ISG化调节Atg7稳定性影响自噬,促进胰腺癌细胞的进展和吉西他滨耐药。 | PANC-1、Mia Paca-2细胞系和BALB/c裸鼠以及人体组织 | 促进 | ||
肿瘤相关巨噬细胞(TAMs)在胰腺癌干细胞(PaCSCs)分泌的IFN-β刺激下释放游离ISG15,促进Erk1/2信号通路的磷酸化,增强了CSCs的干细胞特性及肿瘤的侵袭性。 | 人原代胰腺癌细胞和巨噬细胞细胞系和NU-Foxn1nu裸鼠 | 促进 | ||
结直肠癌 | ISG15基因在结直肠癌的CD133(+)细胞中显著上调。 | 人体组织 | - | |
AIM2通过介导IFN-γ依赖和非依赖的ISGs,包括ISG15,影响MHCⅡ类抗原的表达,揭示了IFN/AIM2/ISG信号通路抑制结直肠癌肿瘤发生。 | HCT116、HT-29、LoVo、KM12、SW480、LS174T、LS180、RKO、Vaco-432、Caco-2细胞系 | 抑制 | ||
糖蛋白90K通过ISG化途径促进β-catenin降解,抑制Wnt信号,抑制肿瘤进展。 | 293T、HCT116、Caco2、CT-26细胞系和BALB/c裸鼠以及人体组织 | 抑制 | ||
USP18缺失调控的ISG化增强增加肿瘤细胞抗原性和放射敏感性。 | HAP1、HCT116细胞系 | 抑制 | ||
USP18通过靶向ISG15修饰的ERK-MNK信号通路发挥致癌作用。 | B16F10、MC38细胞系和C57BL/6小鼠 | 抑制 | ||
ISG化修饰影响UBE2N的泛素化活性,参与调控全反式维甲酸(ATRA)诱导的结肠癌细胞应答。 | HCT-15细胞系 | 抑制 | ||
ISG15 诱导L1细胞黏附分子蛋白的表达,介导结直肠癌的转移。 | LS174T细胞系和NU-Foxn1nu裸鼠 | 促进 | ||
ISG15 减少结直肠癌细胞凋亡并促进细胞存活。 | HT-29细胞系和ApcMin/+小鼠模型 | 促进 | ||
喉癌 | miR-370通过靶向ISG15 mRNA的3'-UTR抑制其蛋白表达,恢复IFN-α信号并促进细胞凋亡,进而抑制喉癌细胞的增殖和侵袭,而ISG15的过表达可部分逆转miR-370的抑制作用。 | LSC-1细胞系和人体组织 | 促进 | |
口腔癌 | 槲皮素的干预能够降低ISG15 表达,抑制细胞迁移和侵袭。 | SCC-15 细胞系 | 促进 |
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