Estrogen 17β-estradiol accelerates the proliferation of uterine junctional zone smooth muscle cells via the let-7a/Lin28B axis in adenomyosis

The estrogen 17 beta-estradiol has been proven to serve an indispensable role in the occurrence and development of adenomyosis (ADS). The let-7a/Lin28B axis can control cell proliferation by acting as a tumor-inhibiting axis in numerous types of cancer. However, its role in ADS remains unknown. The present study aimed i) to elucidate the role of let-7a in regulating the proliferation of human uterine junctional zone (JZ) smooth muscle cells (SMCs) in ADS, ii) to evaluate whether 17 beta-estradiol modifies the expression levels of let-7a and Lin28B in JZ SMCs in ADS, and iii) to establish how 17 beta-estradiol affects the function of the let-7a/Lin28B axis in the proliferation of JZ SMCs in ADS. A total of 36 premenopausal women with ADS were enrolled as the experimental group and 34 women without ADS were recruited as the control group. Reverse transcription-quantitative PCR was used to evaluate the expression level of let-7a, and western blotting was performed to determine the Lin28B expression levels. Lentiviral null vector, let-7a overexpression lentiviral vector GV280 and let-7a inhibition lentiviral vector GV369 were used to infect cells to alter the expression of let-7a for further functional experiments. 17 beta-estradiol and Cell Counting Kit-8 assays were conducted to determine how 17 beta-estradiol affects the function of the let-7a/Lin28B axis in the proliferation of JZ SMCs in ADS. The results demonstrated that let-7a was downregulated and Lin28B was upregulated in the JZ SMCs of ADS compared with the control cells (P<0.0001). Moreover, a lower expression of let-7a led to faster proliferation of JZ SMCs (P<0.05), and 17 beta-estradiol affected the let-7a/Lin28B axis to accelerate the proliferation of JZ SMCs in ADS (P<0.05). These data suggested that 17 beta-estradiol collaborates with the let-7a/Lin28B axis to affect the development of ADS.