Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma.
Targeting stroma and tumor, silencing galectin 1 treats orthotopic mouse hepatocellular carcinoma.
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DOI：
10.1016/j.apsb.2023.10.010
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发表时间：
2024-01
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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本研究探讨了抑制半乳糖凝集素1（Gal 1）作为肝细胞癌（HCC）的治疗选择。Gal 1具有免疫抑制和促癌作用。我们的数据表明，Gal 1在人和小鼠肝癌中高表达。Gal 1水平与人HCC的分期呈正相关，与生存率呈负相关。Gal 1在HCC中的作用使用过表达（OE）或使用由AAV 9递送的Igals 1 siRNA的沉默来研究。在由RAS和AKT突变诱导的HCC起始之前，Igals 1-OE和沉默对肿瘤负荷具有相反的影响。当肿瘤负荷已经达到体重的9%甚至42%时，通过在不同时间点交叉HCC进一步证明lgals 1 siRNA的治疗效果。比较Gal 1沉默和OE HCC的空间转录组学特征，抑制基质形成和位于肿瘤边缘的CD 45+细胞富集区域中的外源抗原识别可能有助于Gal 1沉默的抗HCC作用。在肿瘤内，沉默Gal 1抑制翻译起始、延伸和终止。此外，Gal 1沉默增加了肿瘤内的免疫细胞以及扩增的细胞毒性T细胞，并且lgals 1 siRNA的抗HCC作用是CD 8依赖性的。总的来说，Gal 1沉默对于HCC治疗具有很好的潜力。靶向Gal 1可有效预防和治疗HCC，并具有翻译潜力。
This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45+ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment. Targeting Gal1 is effective in preventing as well as treatment of HCC and has translational potential.
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影响因子：
4.6
作者：
Ha, Sang Yun;Choi, Misun;Park, Cheol-Keun
通讯作者：
Park, Cheol-Keun
影响因子：
45.3
作者：
Le, QT;Shi, GY;Koong, AC
通讯作者：
Koong, AC
DOI：
10.1007/978-1-61779-860-3_5
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Kyrylkova, Kateryna;Kyryachenko, Sergiy;Kioussi, Chrissa
通讯作者：
Kioussi, Chrissa
影响因子：
14.5
作者：
Bourboulia D;Stetler-Stevenson WG
通讯作者：
Stetler-Stevenson WG
影响因子：
6
作者：
Hu, Ying;Zhan, Qi;Wan, Yu-Jui Yvonne
通讯作者：
Wan, Yu-Jui Yvonne