Department of Hematology, Taian City Central Hospital, Taian, Shandong, PR China.
Department of Hematology, Taian City Central Hospital, Taian, Shandong, PR China.
Leuk Res. 2022 Jan;112:106769. doi: 10.1016/j.leukres.2021.106769. Epub 2021 Nov 29.
Diffuse large B cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma worldwide, is aggressive and highly heterogeneous. MiR-665 was found to be lowly expressed in serum exosomes of DLBCL patients and in DLBCL cell lines, but its function in DLBCL progression remains unclear. In this study, miR-665 was overexpressed in SU-DHL-4 cells via miR-665 mimics and knocked down in FARAGE cells via miR-665 inhibitor. Knockdown of miR-665 promoted DLBCL cell proliferation and invasion and decreased cell apoptosis, whereas miR-665 overexpression showed opposite effects on DLBCL cell malignant behaviors. Luciferase reporter assay confirmed LIM and SH3 protein 1 (LASP1) and MYC as target genes of miR-665. Moreover, the expression of LASP1 was negatively correlated with that of miR-665 in LDLBCL cells. LASP1 has tumor-promoting property and its inhibition abolished the effect of miR-665 knockdown on DLBCL cell proliferation, invasion, and apoptosis. SU-DHL-4 cells were inoculated into the flank of nude mice, followed by orthotopic injection with miR-665 agomir. MiR-665 overexpression restricted tumor growth in vivo. Thus, we demonstrates that miR-665 suppresses DLBCL cell malignant behaviors by inhibiting cell proliferation and invasion and inducing apoptosis via targeting LASP1 and MYC, suggesting the importance of miR-665 in DLBCL progression.
弥漫性大 B 细胞淋巴瘤(DLBCL)是全球最常见的非霍奇金淋巴瘤类型,具有侵袭性和高度异质性。研究发现,miR-665 在 DLBCL 患者血清外泌体和 DLBCL 细胞系中低表达,但在 DLBCL 进展中的作用尚不清楚。在这项研究中,通过 miR-665 模拟物在 SU-DHL-4 细胞中过表达 miR-665,并通过 miR-665 抑制剂在 FARAGE 细胞中敲低 miR-665。miR-665 的敲低促进了 DLBCL 细胞的增殖和侵袭,减少了细胞凋亡,而 miR-665 的过表达对 DLBCL 细胞恶性行为则表现出相反的影响。荧光素酶报告基因检测证实 LIM 和 SH3 蛋白 1(LASP1)和 MYC 是 miR-665 的靶基因。此外,LASP1 在 DLBCL 细胞中的表达与 miR-665 的表达呈负相关。LASP1 具有促进肿瘤的特性,其抑制作用消除了 miR-665 敲低对 DLBCL 细胞增殖、侵袭和凋亡的影响。将 SU-DHL-4 细胞接种到裸鼠的侧腹,然后进行 miR-665 激动剂的原位注射。miR-665 的过表达限制了体内肿瘤的生长。因此,我们证明了 miR-665 通过抑制细胞增殖和侵袭,诱导细胞凋亡,靶向 LASP1 和 MYC 抑制 DLBCL 细胞恶性行为,提示 miR-665 在 DLBCL 进展中的重要性。