Protein 14-3-3γ was significantly reduced in human uterine leiomyoma compared to the adjacent normal myometrium tissue. To investigate the possible link between the reduced 14-3-3γ expression and uterine leiomyoma growth, we have overexpressed 14-3-3γ protein in uterine leiomyomal cells and its effects on cell proliferation and apoptosis were analyzed. Over-expression of 14-3-3γ was achieved by transducing into two types of uterine leiomyoma cells (primary culture cells and immortal stem cells) with a 14-3-3γ expressing adenovirus vector. Differentially expressed proteins were screened by the proteomics tool (TMT-LCTMS), followed by PANTHER database analysis to single out specifically modified signaling pathway proteins, which were confirmed by Phospho-MAPK Antibody Array and Western blots analysis. The results showed that increase in 14-3-3γ expression in both two types of human uterine leiomyoma cells inhibited cell proliferation and induced apoptosis. Proteomic screening has found 42 proteins, among 5846, that were significantly affected. PANTHER database and GeneMANIA analysis of the differentially expressed proteins have found that proteins involved in apoptosis signaling and cytoskeletal/adhesion were among the ones affected the most. Further analysis of the key signaling pathways have found that over-expression of 14-3-3γ resulted in reductions in the phosphorylations of multiple signaling molecules, including AKT, pan, ERK1/2, GSK-3 α/β, MEK1/2, Foxo1 and Vimentin. In conclusion, the loss of 14-3-3γ may have causal effects on the growth of uterine leiomyoma, which may function through modifying multiple signaling pathways, including AKT-Foxo and/or MEK1/2-ERK1/2.

与邻近的正常子宫肌层组织相比，人子宫平滑肌瘤中的蛋白质14-3-3γ明显减少。为了研究减少的14-3-3γ表达与子宫平滑肌瘤生长之间的可能联系，我们在子宫平滑肌细胞中过表达了14-3-3γ蛋白，并分析了其对细胞增殖和凋亡的影响。通过用表达14-3-3γ的腺病毒载体转导到两种类型的子宫平滑肌瘤细胞（原代培养细胞和永生干细胞）中来实现14-3-3γ的过表达。通过蛋白质组学工具（TMT-LCTMS）筛选差异表达的蛋白质，然后进行PANTHER数据库分析，以筛选出特定修饰的信号通路蛋白，并通过Phospho-MAPK Antibody Array和Western blot分析证实了这一点。结果表明，两种类型的人子宫平滑肌瘤细胞中14-3-3γ表达的增加均抑制了细胞增殖并诱导了细胞凋亡。蛋白质组学筛查发现5846种蛋白质中有42种受到显着影响。PANTHER数据库和GeneMANIA对差异表达蛋白质的分析发现，与细胞凋亡信号传导和细胞骨架/粘附有关的蛋白质是受影响最大的蛋白质之一。对关键信号通路的进一步分析发现，过量表达14-3-3γ会导致多种信号分子（包括AKT，pan，ERK1 / 2，GSK-3α/β，MEK1 / 2， Foxo1和波形蛋白。总之，丢失14-3-3γ可能对子宫平滑肌瘤的生长具有因果关系，可能通过修饰多种信号传导途径发挥作用，