Micro RNA-98 interferes with expression interleukin-10 in peripheral B cells of patients with lung cancer

Abstract

Interleukin (IL)-10-producing B cells (B10 cells) plays an important role in the tumor tolerance. High frequency of peripheral B10 cell was reported in patients with lung cancer recently. Micro RNA (miR) regulates some gene expression. This study test a hypothesis that miR-98 suppresses the expression of IL-10 in B cells of subjects with lung cancer. The results showed that the levels of miR-98 were significantly less in peripheral B cells of patients with lung cancer than that in healthy subjects. IL-10 mRNA levels in peripheral B cells were significantly higher in lung cancer patients as compared with healthy controls. A negative correlation was identified between miR-98 and IL-10 in peripheral B cells. Serum IL-13 was higher in lung cancer patients than that in healthy controls. The levels of IL-13 were also negatively correlated with IL-10 in B cells. Exposure B10 cells to IL-13 in the culture or over expression of miR-98 reduced the expression of IL-10 in B cells. Administration with miR-98-laden liposomes inhibited the lung cancer growth in a mouse model. In conclusion, up regulation of miR-98 inhibits the expression of IL-10 in B cells, which may contribute to inhibit the lung cancer tolerance in the body.

Figure 1. Peripheral B10 cells are more in patients with lung cancer.

(A) the gated dot plots indicate the frequency of B10 cells in PBMCs of healthy subjects (n = 10) and patients with lung cancer (n = 10). (B) the dot plots show the individual value distribution of panel A.

Figure 2. Assessment of miR-98 and IL-10 mRNA in peripheral B cells.

(A) the histogram shows the purity of B cells isolated from PBMCs, which were isolated from the peripheral blood samples collected from healthy subjects (n = 10) and patients with lung cancer (n = 10). (B,C) the dispersed dot plots show the levels of miR-98 (B) and IL-10 mRNA in the isolated peripheral B cells. (D) the curves show the correlation of individual data between miR-98 and IL-10.

Figure 3. MiR-98 inhibits IL-10 expression in B cells.

B cells were collected from healthy subjects. (A) the bars indicate the miR-98 levels in B cells after treatment with saline or miR-98 plasmids or control plasmids. (B) the bars indicate the IL-10 mRNA in the B cells after the treatment denoted on the X axis. Data of bars are presented as mean ± SD. *p < 0.01, compared with the saline group. The data were summarized from 3 independent experiments.

Figure 4. MiR-98-carrying liposomes inhibit B10 cells and suppress tumor growth.

(A) the scatter plots show the tumor size in individual mice on day 12. (B) the scatter plots show the frequency of peripheral B10 cells. (C) the gated dot plots show the representative results of panel B. Each group consists of 10 mice.