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To investigate the effect of the tripartite motif containing 31 (TRIM31) gene silencing on the proliferation and apoptosis of multiple myeloma cells and its possible mechanism.The normal bone marrow plasma cells (nPCs) were selected as control, and the mRNA and protein expression levels of TRIM31 in human multiple myeloma cell lines (U266, RPMI-8226, NCI-H929 and KMS-11) were detected by RT-qPCR and Western blot. Recombinant lentivirol vector containing shRNA-TRIM31 and its negative control were used to infect U266 cells respectively, and the mRNA expression level of TRIM31 in infected cells was detected by RT-qPCR. Then cell proliferation, colony forming and apoptosis were analyzed by CCK-8, soft agar assay, and flow cytometry, respectively. The protein expression levels of TRIM31, cleaved-caspase-3, BCL-2, Bax, p-Akt (Ser473), Akt and PI3K (p110α) were evaluated by Western blot. In addition, the PI3K/Akt signaling pathway-specific inhibitor LY294002 and TRIM31-shRNA lentivirus were used to interfere with U266 cells, and the cell proliferation, apoptosis, and protein expression of p-Akt (Ser473) and Akt were detected by CCK-8, flow cytometry and Western blot, respectively.Compared with nPCs, the expression levels of TRIM31 mRNA and protein in U266, RPMI-8226, NCI-H929 and KMS-11 cells were significantly increased (P0.001), especially in U266 cells. After lentivirus infection, the levels of TRIM31 mRNA and protein in U266 cells were significantly decreased (P0.001). TRIM31 silencing significantly inhibited the proliferation of U266 cells (P0.05), attenuated the ability of cell cloning, improved cell apoptosis, up-regulated the protein expressions of cleaved-caspase-3 and Bas as well as down-regulated expressions of BCL-2, p-Akt (Ser473) and PI3K (p110α). There was no significant effect on Akt protein. Intervention of LY294002 significantly enhanced the inhibition on cell proliferation and the promotion on apoptosis mediated by TRIM31 gene silencing in U266 cells.TRIM31 gene silencing can inhibit U266 cell proliferation and promote its apoptosis, which may be closely related to inhibition of PI3K/Akt signaling pathway.TRIM31基因沉默对U266细胞增殖及凋亡的影响及其机制.探讨三结构域蛋白31（TRIM31）基因沉默对多发性骨髓瘤细胞增殖及凋亡的影响及其可能机制.以正常人骨髓浆细胞为对照，用RT-qPCR和Western blot实验检测人多发性骨髓瘤细胞株（U266、RPMI-8226、NCI-H929和KMS-11）中TRIM31 mRNA和蛋白表达水平。用RT-qPCR法检测含有shRNA-TRIM31的重组慢病毒载体及其对照载体感染之U266细胞中TRIM31 mRNA的水平；用CCK-8、软琼脂克隆形成实验和流式细胞术分别检测细胞增殖活性、克隆形成能力和凋亡率；Western blot检测细胞中TRIM31、cleaved-caspase-3、BCL-2、Bax、p-Akt（Ser473）、Akt和PI3K（p110α）等蛋白的表达水平。用PI3K/Akt信号通路特异性抑制剂LY294002和TRIM31-shRNA慢病毒联合干预U266细胞，用CCK-8、流式细胞术检测细胞增殖活性和凋亡率，Western blot检测细胞中p-Akt（Ser473）和Akt蛋白表达水平.与正常人骨髓浆细胞比较，U266、RPMI-8226、NCI-H929和KMS-11细胞中TRIM31 mRNA和蛋白表达水平显著升高（P0.001），其中U266细胞最为显著；慢病毒感染后，U266细胞中TRIM31 mRNA和蛋白水平显著降低（P0.001）；沉默TRIM31可显著抑制U266细胞增殖（P0.05），降低细胞克隆形成能力，提高细胞凋亡率，并上调cleaved-caspase-3和Bax蛋白水平，下调BCL-2、p-Akt（Ser473）和PI3K（p110α）蛋白水平，而对Akt蛋白无显著影响；LY294002干预显著增强TRIM31基因沉默对U266细胞增殖的抑制作用以及细胞凋亡的促进作用.TRIM31基因沉默可抑制U266细胞增殖，并促进其凋亡，其机制可能与PI3K/Akt信号通路抑制有关.

Background Chronic myeloid leukemia (CML) is a type of cancer that starts in certain blood-forming cells of the bone marrow. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well known protooncogene, has be shown to be upregulated in various tumor types, including multiple myeloma. However, the biological function of MALAT1 in CML remains has yet to be explored. This study was designed to investigate the effects of MALAT1 on the physiological processes in CML and its underlying mechanisms, which will be helpful for us to have a better understanding of CML development and progression as well as improved therapeutic method. Methods Recombinant virus construction and infection was performed to overexpress or knockdown the expression of MALAT1. Dual luciferase reporter assay was applied to vetify the interaction between MALAT1 and miR-328. The cell viability and cell cycle were analyzed by CCK-8 assay and flow cytometry, respectively. Quantitative real time PCR and western blotting assays were used to measure the expression of genes and proteins. Results The expression of MALAT1 was significantly increased in CML cells compared with peripheral blood cells from health donors. Silencing of MALAT1 significantly inhibited the proliferation and arrested cell cycle of CML cells by targeting miR-328. Moreover, MALAT1 knockdown enhanced imatinib sensitivity of K562 cells, while silencing of miR-328 abolished this effect. Conclusions These findings indicate that lncRNA MALAT1/miR-328 axis promotes the proliferation and imatinib resistance of CML cells, providing new perspectives for the future study of MALAT1 as a therapeutic target for CML.

Multidrug resistance (MDR) has become the major cause of failure chemotherapy for leukemia and high mortality of leukemia. The study aimed to investigate whether the let-7f mediate the Adriamycin (ADR) resistance of leukemia, and to explore the potential molecular mechanism. Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and the soft agar clone formation assay. Flow cytometry was performed to detected cell cycle and apoptosis. The targeted regulationship was analyzed by dual-luciferase assay. Real-time polymerase chain reaction and Western blot were used to measure the expressions of let-7f, ABCC5, ABCC10, cell cycle-related proteins, and apoptosis-related proteins. The xenograft mouse model was used to conduct the tumor formation assay in vivo. The results demonstrated that the expression of let-7f was lower in multidrug-resistant K562/A02 cell lines compared to that in K562, while ABCC5 and ABCC10 were upregulated. Overexpression of let-7f in K562/A02 cell lines downregulated the ABCC5 and ABCC10 expression, enhanced cell sensitivity to ADR, promoted cell apoptosis, and inhibited cell proliferation. let-7f was proved to negatively regulate ABCC5 and ABCC10. Tumor formation assay further determined that let-7f overexpression increased sensitivity to ADR. Taken together, the let-7f downregulation induced the ADR resistance of leukemia by upregulating ABCC5 and ABCC10 expression. Our study provided a novel perspective to study the mechanism of MDR and a new target for the reversal of MDR.

To study the inhibitory effect of serum containing Fuzheng Jiedu decoction on leukemia multi-drug-resistance K562/A02 cells and its possible mechanism.The MTT method was used to detect the inhibitory rate of K562/AO2 cells treated with serum containing Fuzheng Jiedu decoction; the flow cytometry was used to detect the inhibitory effect of serum containing medicin on growth of K562/AO2 cells and P-gp expression; the Q-PCR was used to assay the BCL-2 mRNA expression; the Western blot was used to detect the BCL-2 protein expression.MTT cytotoxic test showed serum containing Fuzheng Jiedu decoction could inhibit K562/A02 cell growth, and the inhibitory rate increased with the increase of drug concentration; the flow cytometry showed that the serum containing Fuzheng Jiedu decoction could promote K562/A02 cell apoptosis in a concentration-dependent manner. qPCR and Western blot showed that serum containing Fuzheng Jiedu decoction could down-regulate the protein expression of BCL-2. Fuzheng Jiedu decoction could reduce the protein expression of P-gp on the K562/A02 cell membrane.serum containing Fuzheng Jiedu decoction can promote K562/A02 cell apoptosis, its mechanism of inducing apoptosis may be related with the inhibition of BCL-2 and P-gp protein expression.