Silencing of augmenter of liver regeneration inhibited cell proliferation and triggered apoptosis in U266 human multiple myeloma cells.

Augmenter of liver regeneration (ALR) is a thermostable cytokine that was originally identified to promote the growth of hepatocytes. This study was conducted to explore the expression and function of ALR in multiple myeloma (MM), a common hematologic malignancy. Real-time PCR and western blot analysis were performed to detect the expression of ALR in U266 human MM cells and healthy peripheral blood mononuclear cells (PBMCs). U266 MM cells were exposed to 20 or 40 µg/mL of recombinant ALR and tested for cell proliferation. Small interfering RNA-mediated silencing of ALR was done to investigate the role of ALR in cell proliferation, apoptosis, and cytokine production. Compared to PBMCs, U266 MM cells exhibited significantly higher levels of ALR at both the mRNA and protein levels. The addition of recombinant ALR protein significantly promoted the proliferation of U266 cells. In contrast, knockdown of ALR led to a significant decline in the viability and proliferation of U266 cells. Annexin-V/PI staining analysis demonstrated that ALR downregulation increased apoptosis in U266 MM cells, compared to control cells (20.1±1.1 vs 9.1±0.3%, P<0.05). Moreover, ALR depletion reduced the Bcl-2 mRNA level by 40% and raised the Bax mRNA level by 2-fold. Additionally, conditioned medium from ALR-depleted U266 cells had significantly lower concentrations of interleukin-6 than control cells (P<0.05). Taken together, ALR contributed to the proliferation and survival of U266 MM cells, and targeting ALR may have therapeutic potential in the treatment of MM.

The +252A/G polymorphism in the Lymphotoxin-α gene and the risk of non-Hodgkin lymphoma: a meta-analysis.

BACKGROUND AND OBJECTIVES: Many studies have shown that the +252A/G polymorphism in the lymphotoxin-α gene is implicated in susceptibility to non-Hodgkin lymphoma but with considerable variance of results. This study aimed to clarify the overall association between the +252A/G polymorphism in the lymphotoxin-α gene and non-Hodgkin lymphoma (NHL) risk by performing a meta-analysis. MATERIALS AND METHODS: The Pubmed and Embase databases were searched for all studies relating to lymphotoxin-α +252A/G gene polymorphism and NHL risk. Data were retrieved and statistical analyses were performed using the Revman 5.1 and STATA 12.0 software. RESULTS: Fourteen case-control studies with 25,098 subjects were included. There was no significant association between lymphotoxin-α +252A/G gene polymorphism and the risk of NHL in the all-combined analysis (OR = 1.08, 95%CI: 0.98-1.19 for GG+GA vs. AA; OR = 1.05, 95%CI: 0.95-1.25 for GG vs. GA+AA). In a subgroup analysis by ethnicity, increased NHL risk was found in North Americans (OR = 1.21, 95%CI: 1.05-1.39 for GG+GA vs. AA), no significant association with NHL risk was identified in Asians or Europeans; In a subgroup analysis by NHL subtype, a significantly increased risk was identified in diffuse large B cell lymphoma patients (OR = 1.20 95%CI: 1.11-1.29 for GG+GA vs. AA), but not for follicular lymphoma. CONCLUSIONS: This meta-analysis suggested that the lymphotoxin-α +252A/G gene polymorphism is a risk factor for NHL in North Americans, and this polymorphism may contribute to diffuse large B cell lymphoma susceptibility. Future studies that include different types of NHL and ethnicities are needed to support and extend these observations.