Department of Gynecology of Traditional Chinese Medicine, China-Japan Friendship Hospital, Beijing, China.
Department of Gynecology of Traditional Chinese Medicine, China-Japan Friendship Hospital, Beijing, China.
Life Sci. 2020 Sep 15;257:118101. doi: 10.1016/j.lfs.2020.118101. Epub 2020 Jul 15.
Uterine leiomyoma (UM) is the most common benign gynecological tumor and the leading indication for hysterectomy. Our study explored the roles of TRIM9 in leiomyoma formation and investigated the underlying molecular mechanisms.
The relationship between TRIM9 expression and fibroids formation was deciphered from the GEO database after bioinformatics analysis and identified by qPCR in human leiomyoma tissues. Both TRIM9 mRNA and protein expression were further detected in primary cultured uterine leiomyoma cells (UMC). The tumorigenesis potentials of TRIM9 in cell proliferation, cell cycle, cell apoptosis; cyclin D1, survivin and cleaved-caspase 3 protein expressions in primary UMC with TRIM9 overexpression (UMC-oeTRIM9); and uterine smooth muscle cells (SMC) with TRIM9 knockdown (SMC-siTRIM9) were evaluated in vitro. NF-κB p65 and its phosphorylation were further examined by western blotting, and rescue experiments on cell proliferation, cell cycle and cell apoptosis were conducted.
TRIM9 showed higher expression in UM tissue and UMC compared with normal myometrium. The overexpression of TRIM9 in UMC notably promoted UM growth via enhancement of cell proliferation, reduction of cell apoptosis, and regulation of cyclin D1, survivin, cleaved-caspase 3, and nuclear NF-κB expression, which were reversed in SMC-siTRIM9 and PDTC (an NF-κB inhibitor) intervention in UMC-oeTRIM9.
To our knowledge, this was the first study demonstrating the roles of TRIM9 in cell growth progression of UM development. TRIM9 may be a potential therapeutic target for UM, by promoting leiomyoma cell proliferation and reducing cell apoptosis via activation of the NF-κB pathway.
子宫肌瘤（UM）是最常见的良性妇科肿瘤，也是子宫切除术的主要指征。本研究探讨了 TRIM9 在肌瘤形成中的作用，并研究了潜在的分子机制。
通过生物信息学分析从 GEO 数据库中破译 TRIM9 表达与纤维瘤形成的关系，并在人子宫肌瘤组织中通过 qPCR 进行鉴定。在原代培养的子宫平滑肌瘤细胞（UMC）中进一步检测 TRIM9 mRNA 和蛋白表达。在转染 TRIM9 过表达载体（UMC-oeTRIM9）的 UMC 和敲低 TRIM9 表达载体（SMC-siTRIM9）的细胞增殖、细胞周期、细胞凋亡、cyclin D1、survivin 和 cleaved-caspase 3 蛋白表达以及 NF-κB p65 及其磷酸化水平检测 TRIM9 在细胞中的致瘤潜能。通过 Western blot 进一步检测 NF-κB p65 及其磷酸化水平，并进行细胞增殖、细胞周期和细胞凋亡的拯救实验。
TRIM9 在 UM 组织和 UMC 中的表达均高于正常子宫肌层。在 UMC 中转染 TRIM9 显著促进了 UM 的生长，通过增强细胞增殖、减少细胞凋亡以及调节 cyclin D1、survivin、cleaved-caspase 3 和核 NF-κB 表达来实现，这在 SMC-siTRIM9 和 PDTC（NF-κB 抑制剂）干预 UMC-oeTRIM9 中得到了逆转。
据我们所知，这是第一项研究表明 TRIM9 在 UM 发展中细胞生长进展中的作用。TRIM9 可能是 UM 的潜在治疗靶点，通过激活 NF-κB 通路促进子宫肌瘤细胞增殖和减少细胞凋亡。
