Department of Oncology, The First Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, 130000, Jilin, China.
Hematology of Cancer Center, The First Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, 130000, Jilin, China.
Cell Biol Int. 2020 Jun;44(6):1331-1340. doi: 10.1002/cbin.11327. Epub 2020 Apr 3.
Diffuse large B-cell lymphoma (DLBC) is a subtype of lymphoma with the worst prognosis. Existing treatment methods are not effective enough due to its high occurrence of metastasis. Therefore, identification of effective therapeutic targets is becoming increasingly important. In this research, long non-coding RNA dopamine β hydroxylase antisense RNA 1 (DBH-AS1) was found to be upregulated in DLBC tissues and cells. Knockdown of DBH-AS1 suppressed the proliferation, migration, and invasion of cancer cells. Afterwards, RNA-binding protein BUD13 homolog (BUD13) was found to be upregulated in cancer tissues and cells while binding to DBH-AS1. Fibronectin 1 (FN1) was the downstream messenger RNA (mRNA) of BUD13. FN1 was upregulated in DLBC and was positively correlated with DBH-AS1. Further rescue assays proved that DBH-AS1 mediated FN1 expression by recruiting BUD13. In the meantime, BUD13 stabilized FN1 mRNA to promote FN1 expression. In this way, DBH-AS1/BUD13/FN1 axis was confirmed. A set of rescue assays proved that DBH-AS1 regulated DLBC progression via BUD13 and FN1. The function and mechanism of DBH-AS1 were investigated for the first time in DLBC. DBH-AS1 might become a therapeutic target in lymphoma treatment in the future.
弥漫性大 B 细胞淋巴瘤（DLBC）是一种预后最差的淋巴瘤亚型。由于其高转移率，现有的治疗方法效果不够理想。因此，识别有效的治疗靶点变得越来越重要。在这项研究中，发现长链非编码 RNA 多巴胺 β 羟化酶反义 RNA 1（DBH-AS1）在 DLBC 组织和细胞中上调。DBH-AS1 的敲低抑制了癌细胞的增殖、迁移和侵袭。随后，发现 RNA 结合蛋白 BUD13 同源物（BUD13）在癌症组织和细胞中上调，同时与 DBH-AS1 结合。纤连蛋白 1（FN1）是 BUD13 的下游信使 RNA（mRNA）。FN1 在 DLBC 中上调，与 DBH-AS1 呈正相关。进一步的挽救实验证明，DBH-AS1 通过招募 BUD13 介导 FN1 的表达。同时，BUD13 稳定 FN1 mRNA 以促进 FN1 表达。通过这种方式，证实了 DBH-AS1/BUD13/FN1 轴。一系列挽救实验证明，DBH-AS1 通过 BUD13 和 FN1 调节 DLBC 的进展。首次在 DLBC 中研究了 DBH-AS1 的功能和机制。DBH-AS1 可能成为未来淋巴瘤治疗的一个治疗靶点。
