Up-regulation of stathmin by specialized protein 1 promotes proliferation and inhibits apoptosis in uterine leiomyoma cells

Abstract

Objective To study the effect of microtubule depolymerization protein 1 (stathmin, STMN1) on the proliferation and apoptosis of uterine leiomyomas cells under the transcriptional regulation of specialized protein 1 (SP1). Methods A total of 30 patients of uterine leiomyomas undergoing total and subtotal hysterectomy in our hospital from June 2017 to June 2019 were recruited in this study. The mRNA expression levels of STMN1 and SP1 in the uterine leiomyoma tissues and surrounding smooth muscle tissues were detected with qRT-PCR. After STMN1 was knocked down in human uterine leiomyoma (HuLM) cells, CCK8 assay, TUNEL and Western blotting were used to detect the cell proliferation and apoptosis. JASPAR online tool was employed to predict the binding site of transcription factor SP1 and STMN1 promoter. qRT-PCR, Western blotting, luciferase reporter assay, and chromatin immunoprecipitation (ChIP) were applied to verify the transcriptional regulation of SP1 for STMN1, and functional rescue experiments were also carried out. Results The expression levels of STMN1 and SP1 were significantly higher in the uterine leiomyoma tissues than the normal smooth muscle tissues (P < 0.05). Knockdown of STMN1 inhibited the proliferation and promoted the apoptosis in HuLM cells (P < 0.001). SP1, as a transcription factor, positively regulated the expression level of STMN1. Knockdown of SP1 could also inhibit the proliferation and promote the apoptosis of HuLM cells (P < 0.001), and overexpression of STMN1 reversed the effect of knockdown of SP1 on cell proliferation and apoptosis (P < 0.001). Conclusion The transcription factor SP1 promotes the proliferation and inhibits the apoptosis in the uterine leiomyoma cells by up-regulating STMN1.

Keywords

• uterine leiomyoma
• stathmin
• transcription factor
• specialized protein 1
• proliferation
• apoptosis