Delivery of LINC00589 via mesoporous silica nanoparticles inhibits peritoneal metastasis in gastric cancer.
Delivery of LINC00589 via mesoporous silica nanoparticles inhibits peritoneal metastasis in gastric cancer.
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DOI：
10.1016/j.canlet.2022.215916
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发表时间：
2022-09
期刊：
影响因子：
9.7
通讯作者：
Shuchang Wang;Lulu Wo;Zizhen Zhang;Chunchao Zhu;Chaojie Wang;Yangyang Wang;Lechun Hou;H. Cao-H.-Ca
中科院分区：
文献类型：
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作者：
Shuchang Wang;Lulu Wo;Zizhen Zhang;Chunchao Zhu;Chaojie Wang;Yangyang Wang;Lechun Hou;H. Cao-H.-Ca
腹膜转移是胃癌（GC）常见的转移形式之一。在本研究中，我们鉴定了 GC 患者中 LINC00589 的表达模式，并研究了 GC 细胞中的生物学功能。进行 RNA 下拉实验以探索潜在的分子机制。此外，我们利用聚乙烯亚胺修饰的介孔二氧化硅纳米颗粒（PMSN）作为纳米载体来递送LINC00589编码质粒，并测试了其对腹膜传播的GC的治疗潜力。我们发现LINC00589在GC组织中下调并抑制GC细胞的转移能力。从机制上讲，LINC00589通过促进hnRNPA1蛋白泛素化和蛋白酶体降解，从而阻断PKM与PKM2的选择性剪接来发挥肿瘤抑制功能。此外，PMSNs递送的LINC00589可以在体内和体外抑制GC的腹膜转移。该工作可能为GC腹膜转移提供新的治疗选择。
Peritoneal metastasis is one of the common forms of metastasis in gastric cancer (GC). In this study, we identified the expression pattern of LINC00589 in GC patients and investigate the biological function in GC cells. RNA-pulldown assay was performed to explore the underlying molecular mechanism. Further, we utilize polyethyleneimine-modified mesoporous silica nanoparticles (PMSNs) as the nanocarriers for delivery of LINC00589 encoding plasmid and tested its therapeutic potential for GC with peritoneal dissemination. We revealed that LINC00589 was downregulated in GC tissues and suppressed the metastatic ability of GC cells. Mechanistically, LINC00589 exerted tumor suppressive function by promoting hnRNPA1 protein ubiquitination and proteasomal degradation, thus blocking alternative splicing of PKM to PKM2. Furthermore, LINC00589 delivered by PMSNs could suppress the peritoneal metastasis of GCin vivoandin vitro. This work may provide a new treatment option in GC peritoneal metastasis.