BST2 通过调控 HOXD9 和 PABPC1 促进胃癌转移。

BST2 promotes gastric cancer metastasis under the regulation of HOXD9 and PABPC1.

机构信息

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Gastroenterology, The Key Laboratory of Advanced Interdisciplinary Studies Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

出版信息

Mol Carcinog. 2024 Apr;63(4):663-676. doi: 10.1002/mc.23679. Epub 2024 Jan 10.

DOI:10.1002/mc.23679

PMID:38197534

Abstract

Gastric cancer (GC) constitutes substantial cancer mortality worldwide. Several cancer types aberrantly express bone marrow stromal cell antigen 2 (BST2), yet its functional and underlying mechanisms in GC progression remain unknown. In our study, RNA sequencing data revealed that BST2 was transcriptionally activated by homeobox D9 (HOXD9). BST2 was significantly upregulated in GC tissues and promoted epithelial-mesenchymal transition and metastasis of GC. BST2 knockdown reversed HOXD9's oncogenic effect on GC metastasis. Moreover, BST2 messenger RNA stability could be enhanced by poly(A) binding protein cytoplasmic 1 (PABPC1) through the interaction between BST2 3'-UTR and PABPC1 in GC cells. PABPC1 promoted GC metastasis, which BST2 silencing attenuated in vitro and in vivo. In addition, positive correlations among HOXD9, BST2, and PABPC1 were established in clinical samples. Taken together, increased expression of BST2 induced by HOXD9 synergizing with PABPC1 promoted GC cell migration and invasion capacity.

摘要

胃癌（GC）在全球范围内构成了大量的癌症死亡。几种癌症类型异常表达骨髓基质细胞抗原 2（BST2），但其在 GC 进展中的功能和潜在机制尚不清楚。在我们的研究中，RNA 测序数据显示，BST2 被同源盒 D9（HOXD9）转录激活。BST2 在 GC 组织中显著上调，并促进了 GC 的上皮-间充质转化和转移。BST2 敲低逆转了 HOXD9 对 GC 转移的致癌作用。此外，在 GC 细胞中，BST2 的 3'UTR 和 PABPC1 之间的相互作用可以增强多聚（A）结合蛋白细胞质 1（PABPC1）对 BST2 信使 RNA 稳定性的影响。PABPC1 促进了 GC 转移，而 BST2 沉默则减弱了这种转移，无论是在体外还是体内。此外，在临床样本中建立了 HOXD9、BST2 和 PABPC1 之间的正相关关系。综上所述，HOXD9 协同 PABPC1 诱导的 BST2 表达增加促进了 GC 细胞的迁移和侵袭能力。