干扰素γ诱导蛋白16（IFI16）在多发性骨髓瘤中的功能研究.

Objective: To reveal the function of interferon gamma inducible protein 16 (IFI16) in multiple myeloma (MM) . Methods:Human multiple myeloma cells (RPMI-8266) were divided into Control group (untransfected cells), NC-sh group (cells transfected with negative control shRNA lentivirus), IFI16-sh group (cells transfected with IFI16 shRNA lentivirus), NC-OE group (cells transfected with negative control overexpressing lentivirus) and IFI16-OE group (cells transfected with IFI16 overexpression lentivirus) . Lipofectamine2000 was used for transfection and cells were collected after 48 h culture. Cell proliferation was detected by MTT assay and colony formation test. Apoptosis was detected by Annexin V-FITC and PI staining. Cell invasion was detected by Transwell. The m RNA levels of IFI16, Bcl-2, Bax, fibroblast growth factor (FGF) 1 and FGF2 were detected by qRT-PCR. The protein expression level of IFI16 was detected by Western blot. Nude mice were randomly divided into NC-sh group and IFI16-sh group (n=6) . Nude mice in NC-sh group and IFI16-sh group were subcutaneously injected with RPMI-8266 cell suspension transfected with NC-sh and IFI16-sh, respectively. After35 days, the tumor volume was measured and the tumor weight was weighed. The levels of Th1 cytokines [interferon-γ (IFN-γ), interleukin (IL) -12], Th2 cytokines (IL-4) and proinflammatory factors [IL-1β, IL-6, tumor necrosis factor-α (TNF-α) ] were detected by ELISA method. Results: Compared with Control group and NC-sh group, the relative expression of IFI16 m RNA and protein of RPMI-8266 cells in IFI16-sh group decreased (P＜0.05), relative cell viability and number of colony and invasive cells decreased (P＜0.05),the apoptosis rate and relative expression of Bax m RNA increased (P＜0.05), the relative m RNA expression level of Bcl-2, FGF1 and FGF2 decreased (P＜0.05) . Compared with Control group and NC-OE group, the relative expression of IFI16 m RNA and protein of RPMI-8266 cells in IFI16-OE group increased (P＜0.05), relative cell viability and number of colony invasive cells increased (P＜0.05), apoptosis rate and relative expression of Bax m RNA decreased (P＜0.05), the relative m RNA expression level of Bcl-2, FGF1 and FGF2 increased (P＜0.05) . Compared with NC-sh group, the tumor volume, tumor weight, the relative expression of IFI16 m RNA and protein in tumor tissue of IFI16-sh group decreased (P＜0.05), the levels of IFN-γ and IL-12 in peripheral blood increased (P＜0.05), the level of IL-4, IL-1β, IL-6 and TNF-α in peripheral blood decreased (P＜0.05) . Conclusion: IFI16 is a kind of oncogene in MM. Down-regulation of IFI16 can inhibit the growth and invasion of MM cells. The mechanism is related to correcting the balance of Th1/Th2 cells and inhibiting the activity of pro-inflammatory factors [ABSTRACT FROM AUTHOR]