The c-Jun and JunB transcription factors facilitate the transit of classical Hodgkin lymphoma tumour cells through G(1).

The c-Jun and JunB transcription factors facilitate the transit of classical Hodgkin lymphoma tumour cells through G(1).
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DOI:
10.1038/s41598-018-34199-9
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发表时间:
2018-10-30
期刊:
影响因子:
4.6
通讯作者:
Ingham RJ
Ingham RJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang J;Wu Z;Savin A;Yang M;Hsu YR;Jantuan E;Bacani JTC;Ingham RJ

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经典霍奇金淋巴瘤 (cHL) 主要是一种 B 细胞淋巴肿瘤,也是 CD30 阳性淋巴瘤的一员。 cHL 和其他 CD30 阳性淋巴瘤的特征是激活蛋白 1 (AP-1) 家族转录因子 c-Jun 和 JunB 表达升高和/或组成型激活;然而,它们在 cHL 病理学中发挥的具体作用尚不清楚。在本报告中,我们表明,用短发夹 RNA (shRNA) 减少 c-Jun 或 JunB 表达可减少 cHL 细胞系在体外和体内的生长,主要是通过损害细胞周期过渡至 G1 期来实现的。我们进一步研究了 c-Jun 和 JunB 敲低对另一种 CD30 阳性淋巴瘤、间变性淋巴瘤激酶阳性、间变性大细胞淋巴瘤 (ALK+ ALCL) 增殖的影响。我们发现,在大多数检查的 ALK+ ALCL 细胞系中,JunB 敲低也会导致与 G0/G1 细胞周期缺陷相关的增殖减少。相比之下,多个 ALK+ ALCL 细胞系中的 c-Jun 敲低对增殖没有影响。总之,本研究直接证实了 c-Jun 和 JunB 在促进 HRS 细胞增殖中发挥作用。此外,我们证明 cHL 和 ALK+ ALCL 之间的 c-Jun 和 JunB 功能存在相似性和差异。
Classical Hodgkin Lymphoma (cHL) is primarily a B cell lymphoid neoplasm and a member of the CD30–positive lymphomas. cHL and the other CD30–positive lymphomas are characterized by the elevated expression and/or constitutive activation of the activator protein-1 (AP-1) family transcription factors, c-Jun and JunB; however, the specific roles they play in the pathobiology of cHL are unclear. In this report we show that reducing either c-Jun or JunB expression with short-hairpin RNAs (shRNAs) reduced the growth of cHL cell lines in vitro and in vivo, primarily through impairing cell cycle transition through G1. We further investigated the effect of c-Jun and JunB knock-down on proliferation in another CD30–positive lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL). We found that JunB knock-down in most ALK+ ALCL cell lines examined also resulted in reduced proliferation that was associated with a G0/G1 cell cycle defect. In contrast, c-Jun knock-down in multiple ALK+ ALCL cell lines had no effect on proliferation. In summary, this study directly establishes that both c-Jun and JunB play roles in promoting HRS cell proliferation. Furthermore, we demonstrate there are similarities and differences in c-Jun and JunB function between cHL and ALK+ ALCL.
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