Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan.
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan.
Biomolecules. 2023 Jan 18;13(2):193. doi: 10.3390/biom13020193.
Uterine leiomyomas are smooth-muscle tumors originating in the myometrium and are the most common pelvic tumors in women of reproductive age. Symptomatic tumors may result in abnormal uterine bleeding, bladder dysfunction, pelvic discomfort, and reproductive issues, such as infertility and miscarriage. There are currently few non-invasive treatments for leiomyoma, but there are no practical early intervention or preventive methods. In this study, human uterine leiomyoma and myometrial tissues were used to detect the protein and mRNA expression levels of UCHL1. To explore the effects of UCHL1 knockdown and inhibition in leiomyoma and myometrial cells, we determined the mRNA expressions of COL1A1 and COL3A1. Collagen gel contraction and wound-healing assays were performed on myometrial and leiomyoma cells. We found that UCHL1 expression was considerably higher in uterine leiomyomas than in the myometrium. COL1A1 and COL3A1 expression levels were downregulated after inhibition of UCHL1 in human leiomyoma cells. Furthermore, the elimination of UCHL1 significantly decreased the migration and contractility of leiomyoma cells. In conclusion, these results indicate that UCHL1 is involved in the growth of leiomyoma in humans. For the treatment of uterine leiomyoma, targeting UCHL1 activity may be a unique and possible therapeutic strategy.
子宫肌瘤是起源于子宫肌层的平滑肌肿瘤，是生育期妇女最常见的盆腔肿瘤。有症状的肿瘤可导致异常子宫出血、膀胱功能障碍、盆腔不适以及生殖问题，如不孕和流产。目前，对于子宫肌瘤的非侵入性治疗方法很少，但实际上并没有早期干预或预防的方法。在本研究中，我们使用人子宫肌瘤和子宫肌组织检测了 UCHL1 的蛋白和 mRNA 表达水平。为了探讨 UCHL1 敲低和抑制对子宫肌瘤和子宫肌细胞的影响，我们测定了 COL1A1 和 COL3A1 的 mRNA 表达。我们对子宫肌细胞和子宫肌瘤细胞进行了胶原凝胶收缩和划痕愈合实验。结果发现，UCHL1 在子宫肌瘤中的表达明显高于子宫肌层。抑制人子宫肌瘤细胞中的 UCHL1 后，COL1A1 和 COL3A1 的表达水平下调。此外，消除 UCHL1 显著降低了子宫肌瘤细胞的迁移和收缩能力。综上所述，这些结果表明 UCHL1 参与了人类子宫肌瘤的生长。针对 UCHL1 活性的治疗可能是一种独特且可行的治疗策略。
