Long non-coding RNA SNHG17 may function as a competitive endogenous RNA in diffuse large B-cell lymphoma progression by sponging miR-34a-5p.

We investigated the functional mechanism of long non-coding small nucleolar host gene 17 (SNHG17) in diffuse large B-cell lymphoma (DLBCL). lncRNAs related to the prognosis of patients with DLBCL were screened to analyze long non-coding small nucleolar host gene 17 (SNHG17) expression in DLBCL and normal tissues, and a nomogram established for predicting DLBCL prognosis. SNHG17 expression in B-cell lymphoma cells was detected using qPCR. The effects of SNHG17 with/without doxorubicin on the proliferation and apoptosis of DoHH2 and Daudi were detected. The effects of combined SNHG17 and doxorubicin were analyzed. The regulatory function of SNHG17 in DLBCL was investigated using a mouse tumor xenotransplantation model. RNA sequencing was used to analyze the signaling pathways involved in SNHG17 knockdown in B-cell lymphoma cell lines. The target relationships among SNHG17, microRNA, and downstream mRNA biomolecules were detected. A higher SNHG17 level predicted a lower survival rate. SNHG17 was highly expressed in DLBCL patient tissues and cell lines. We established a prognostic model containing SNHG17 expression, which could effectively predict the overall survival rate of DLBCL patients. SNHG17 knockdown inhibited the proliferation and induced the apoptosis of B-cell lymphoma cells, and the combination of SNHG17 and doxorubicin had a synergistic effect. SNHG17, miR-34a-5p, and ZESTE gene enhancer homolog 2 (EZH2) had common hypothetical binding sites, and the luciferase reporter assay verified that miR-34a-5p was the direct target of SNHG17, and EZH2 was the direct target of miR-34a-5p. The carcinogenic function of SNHG17 in the proliferation and apoptosis of DLBCL cells was partially reversed by a miR-34a-5p inhibitor. SNHG17 increases EZH2 levels by inhibiting miR-34a-5p. Our findings indicate SNHG17 as critical for promoting DLBCL progression by regulating the EZH2 signaling pathway and sponging miR-34a-5p. These findings provide a new prognostic marker and therapeutic target for the prognosis and treatment of DLBCL.

Biodegradable amphiphilic block copolymers bearing protected hydroxyl groups: synthesis and characterization.

A new biodegradable amphiphilic block copolymer, poly(ethylene glycol)-b-poly(L-lactide-co-9-phenyl-2,4,8,10-tetraoxaspiro[5,5]undecan-3-one) [PEG-b-P(LA-co-PTO)], was successfully prepared by ring-opening polymerization (ROP) of L-lactide (LA) and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraozaspiro[5,5]undecan-3-one (PTO) in the presence of monohydroxyl poly(ethylene glycol) as macroinitiator using Sn(Oct)2 as catalyst. NMR, FT-IR, and GPC studies confirmed the copolymer structure. It could self-assemble into micelles in aqueous solution with critical micelle concentration (CMC) in the magnitude of mg/L, which changed with the composition of the copolymer. After catalytic hydrogenation, copolymers with active hydroxyl groups were obtained. Adhesion and proliferation of Vero cells on the copolymer films showed that the synthesized copolymers were good biocompatible materials. In vitro degradation of the copolymer before and after deprotection was investigated in the presence of proteinase K. The free hydroxyl groups on the copolymers were capable of further modification with biotin. This new amphiphilic block copolymer has great potential for both drug encapsulation and conjugate because of its low CMC and the presence of active hydroxyl groups.

An improved approach to poly(ester-carbonate) conjugates.

A novel poly(ester-carbonate) (P(LA-co-NPC)) with activated pendant carboxyl groups was synthesized by ring-opening polymerization of L-lactide (LA) and 2-methyl-2-(4-nitrophenoxycarbonyl)-propylene carbonate (NPC) with diethyl zinc (ZnEt(2)) as catalyst. GPC and NMR studies confirmed the co-polymer structure. The pendant 4-nitrophenyl carboxylate groups can react with amino-containing molecules, such as 3,6,9-trioxa-1,11-undecanediamine, doxorubicin and chitosan under mild conditions. Therefore, any amino-containing molecules of biomedical interests can be conjugated to P(LA-co-NPC) efficiently and easily. The biocompatibility of the co-polymer was tested using L929 cell line, indicating that P(LA-co-NPC) is a promising biomedical material.

Influence of coupling bonds on the anti-tumor activity of polymer-pirarubicin conjugates.

Pirarubicin (THP) was conjugated onto the pendant carboxyl groups of poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) [PEG-b-P(LA-co-MCC)] through hydrazone, ester, and amide bonds, respectively, and the conjugates were assembled into micelles with diameters between 30 and 60 nm. The in vitro THP release of the three conjugate micelles was conducted in pH 7.4 and 5.0 buffer solutions, and conjugate micelles with hydrazone linkage had the fastest THP release rate. Their in vitro cytotoxicity was tested using mouse mammary adenocarcinoma EMT6 cells and in vivo anti-tumor activity in Balb/c mice models bearing EMT6 tumors were compared with free THP and with each other. The results showed that the polymer-THP conjugates displayed higher cell-uptakes and better anti-tumor activities than free THP at 4h, and among the three micelles, those with hydrazone linkage had the highest anti-tumor activity in vivo, while those with amide linkage were the lowest.