J Cancer 2021; 12(22):6835-6850. doi:10.7150/jca.64031 This issue
1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Liaoning, China.
2. Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Liaoning, China.
3. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
Introduction: Keratin 80 (KRT80) is a type II epithelial keratin protein that plays an important role in cell differentiation and tumor progression. However, its role and mechanisms in ovarian cancer remain unclear.
Methods: The effect of KRT80 on the survival and prognosis of patients with ovarian cancer was determined using immunohistochemistry. Cell lines overexpressing KRT80 and with KRT80 knockdown were established to study its effect on the malignant behavior of ovarian cancer cells. Western blotting was used to detect changes in related molecules, and in the MEK/ERK signal transduction pathway. ChIP assay was used to confirm that ETS1 regulates KRT80 at the transcriptional level. A double luciferase assay was used to confirm the target of miR-206.
Results: The expression levels of KRT80 were high in ovarian cancer tissue, and were related to survival and prognosis. KRT80 expression is an independent prognostic factor in patients with ovarian cancer. KRT80 overexpression promotes the proliferation of ovarian cancer cells, the transition from G1 phase to S phase, invasion, and migration. KRT80 overexpression increased the expression of BCL2/BAX, CyclinD1, MMP2, MMP9, and N-cadherin, decreased the expression of E-cadherin, and increased the phosphorylation of MEK and ERK. ETS1 binds to the upstream promoter sequence of KRT80 and regulates KRT80 expression at the transcriptional level. ETS1 is a direct target of miR-206 in ovarian cancer cells.
Conclusion: KRT80 regulated by miR-206/ETS1 promotes tumor progression via the MEK/ERK pathway in ovarian cancer, and KRT80 may have applications as a screening biomarker and potential therapeutic target for ovarian cancer.
Keywords: ovarian cancer, KRT80, MEK/ERK pathway, ETS1, miR-206