Abstract
The SRY-box containing gene 17 (SOX17) is considered as a regulator in stemness maintenance and a suppressor in some malignant tumors. However, the biological function and molecular mechanism of SOX17 in the process of initiation and progression of cervical cancer remain obscure. In this study, immunohistochemistry showed that the expression of SOX17 was high in the normal cervix, moderate in the high-grade squamous intraepithelial lesion, and low in the cervical cancer. SOX17 inhibited the proliferation and viability of cervical cancer cells in vitro as well as tumor formation in vivo. Additionally, SOX17 induced the cell cycle arrest at the transition from the G0/G1 phase to the S phase. The TOP/ FOP-Flash reporter assay and Western blotting showed SOX17 inhibited the activity of the Wnt/β-catenin signaling pathway in cervical cancer. Further, firefly luciferase reporter assay and quantitative chromatin immunoprecipitation (qChIP) assays confirmed that SOX17 trans-suppressed the expression of β-catenin by directly binding to the specific region of the β-catenin promoter. Together, our data demonstrated that SOX17 restrained the proliferation and tumor formation by down-regulating the activity of the Wnt/β-catenin signaling pathway via trans-suppression of β-catenin in cervical cancer.
Highlights
Cervical cancer is the fourth most common cancer in women and the seventh overall[1]
It showed that 49.3% (33/67) of CC demonstrated reduced SRY-box containing gene 17 (SOX17) expression compared to normal cervix (NC) (6.4%, 2/31) and high-grade squamous intraepithelial lesion (HSIL) (20%, 4/20) (Fig. 1b)
Values are shown as the mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 revealed that SOX17 expression was found in cervical cancer cell lines (Fig. 2a, b and S1A)
Summary
Cervical cancer is the fourth most common cancer in women and the seventh overall[1]. High-risk human papillomavirus (HPV) is well established as the major risk factor for cervical. Li et al Cell Death and Disease (2018)9:741 key role in the generation and maintenance of neonatal hematopoietic stem cells (HSCs)[15] as well as in regulating the fate of human primordial germ cells (PGCs)[16]. SOX17 has been widely studied in cancers, such as breast cancer[17], colorectal cancer[18], hepatocellular carcinoma[19], gastric cancer[20], esophageal cancer[21], cholangiocarcinoma[22], endometrial cancer[23] and cervical cancer[24]. The regulatory function of SOX17 on target genes at the transcriptional level contributing to tumorigenesis is insufficiently understood. The molecular mechanisms of SOX17 in cervical carcinoma initiation and progression are largely unknown
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