Overexpressed miR-195 attenuated immune escape of diffuse large B-cell lymphoma by targeting PD-L1.

Diffuse large B-cell lymphoma (DLBCL) seriously threatens patients life with the morbidity increases at a high rate. Immune response disorder is the potential factor that induces DLBCL, while the potential mechanism still not fully understand. Real-time PCR and western blot were performed to determine genes expression. Flow cytometry was employed to detect the expression of PD-1 and the ratio of PD-1+T cells. Enzyme-linked immune sorbent assay (ELISA) was used to determine the cytokines secretion. MiR-195 was down-regulated, while PD-L1 was up-regulated in DLBCL tissues, and the rate of PD-1+T cells was increased in T cells of peripheral blood in DLBCL. Overexpressed miR-195 suppressed the expression of PD-L1. Moreover, miR-195 overexpression significantly promoted the secretion of IFN-γ and TNF-α, but decreased IL-10 and PD-1+T cells rate in the co-culture model of T cells and OCI-Ly-10 cells. MiR-195 targets PD-L1 to regulate the expression of IFN-γ, TNF-α, IL-10 and the rate of PD-1+T cells. MiR-195 regulated immune response of DLBCL through targeting PD-L1.

He B ，Yan F ，Wu C 《-》

LncRNA MALAT1 promotes tumorigenesis and immune escape of diffuse large B cell lymphoma by sponging miR-195.

PD-L1 enhanced the tumorigenesis and immune escape abilities of cancers. The upstream mechanisms of PD-L1 in regulating tumorigenesis and immune escape of diffuse large B cell lymphoma (DLBCL) remained unclear. Human DLBCL cell line OCI-Ly10 and DLBCL patient samples were used in this study. MALAT1 was knocked down by shRNA. MiR-195 was inhibited by miR-195 inhibitor. Levels of MALAT1, PD-L1, miR-195 and CD8 were detected by RT-qPCR. Protein levels of PD-L1, Ras, p-ERK1/2, ERK1/2, Slug, E-cadherin, N-cadherin, Vimentin were detected by western blotting. The interaction between MALAT1 and miR-195, miR-195 and PD-L1 were detected by luciferase assay. OCI-Ly10 cell proliferation and apoptosis were detected by MTT and Annexin V/PI assays, respectively. Migration was detected by transwell assay. Cytotoxicity of CD8+ T cells was detected by LDH cytotoxicity kit. Proliferation and apoptosis of CD8+ T cell co-cultured with OCI-Ly10 cells were analyzed by CFSE and Annexin V/PI staining. MALAT1, PD-L1 and CD8 were up-regulated in DLBCL tissues while miR-195 was down-regulated. MiR-195 was negatively correlated with MALAT1 and PD-L1. MALAT1 could sponge miR-195 to regulate the expression of PD-L1. shMALAT1 treatment increased miR-195 level and decreased PD-L1 level. It also inhibited cell proliferation, migration and immune escape ability while increased apoptosis ratio of OCI-Ly10 cells. shMALAT1 treatment in OCI-Ly10 cells also promoted proliferation and inhibited apoptosis of CD8+ T cells. Knocking down of MALAT1 also suppressed EMT-like process via Ras/ERK signaling pathway. These effects were all rescued by miR-195 inhibitor. Long non-coding RNA MALAT1 sponged miR-195 to regulate proliferation, apoptosis and migration and immune escape abilities of DLBCL by regulation of PD-L1.

Wang QM ，Lian GY ，Song Y ，Huang YF ，Gong Y ... -  《-》

MiR-214 prevents the progression of diffuse large B-cell lymphoma by targeting PD-L1.

We explored the role and mechanism of miR-214 involvement in the progression of diffuse large B-cell lymphoma (DLBCL). The expression levels of miR-214 and PD-L1 in human DLBCL cell lines and in tissue samples from patients with DLBCL were determined using quantitative RT-PCR. The dual-luciferase reporter assay was employed to determine the correlation between the expressions of miR-214 and PD-L1. Cell viability, invasiveness and apoptosis were respectively examined in cells of the DLBCL line OCI-Ly3 using CCK-8, transwell and flow cytometry assays. The expression level of PD-L1 was determined via immunoblotting. Inflammatory cytokine secretion was determined via enzyme-linked immune sorbent assay (ELISA). miR-214 was downregulated and PD-L1 was upregulated in DLBCL tissues and cell lines in comparison to normal adjacent tissues or normal B-cell. This indicates a negative correlation in the expression levels. Overexpression of miR-214 inhibited cell viability and invasion and induced apoptosis of OCI-Ly3 cells. Moreover, miR-214 was shown to target PD-L1 mRNA by binding to its 3'-untranslated region (UTR). Knockdown of PD-L1 attenuated the malignant phenotype of OCI-Ly3 cells. Overexpression of miR-214 inhibited tumor growth by targeting PD-L1 in vivo. By targeting PD-L1, miR-214 regulates the progression of DLBCL in vitro and in vivo.

Sun JR ，Zhang X ，Zhang Y 《-》

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

Anastasiadou E ，Stroopinsky D ，Alimperti S ，Jiao AL ，Pyzer AR ，Cippitelli C ，Pepe G ，Severa M ，Rosenblatt J ，Etna MP ，Rieger S ，Kempkes B ，Coccia EM ，Sui SJH ，Chen CS ，Uccini S ，Avigan D ，Faggioni A ，Trivedi P ，Slack FJ ... -  《-》

MiR155 sensitized B-lymphoma cells to anti-PD-L1 antibody via PD-1/PD-L1-mediated lymphoma cell interaction with CD8+T cells.

Zheng Z ，Sun R ，Zhao HJ ，Fu D ，Zhong HJ ，Weng XQ ，Qu B ，Zhao Y ，Wang L ，Zhao WL ... -  《Molecular Cancer》