MiR-665 suppresses the progression of diffuse large B cell lymphoma (DLBCL) through targeting LIM and SH3 protein 1 (LASP1)

Abstract

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.