Title : ARID1A inhibits progression of ovarian cancer by inactivating hedgehog pathway
Abstract:
Ovarian cancer is one kind of malignant tumors derived from epithelial and germ cells, and is the second most lethal gynecologic malignancy worldwide. The abnormal activation of the Hedgehog (Hh) pathway is crucial for cancer progression, including ovarian cancer. AT-rich interacting domain-containing protein 1A (ARID1A) is a member of the SWItch/Sucrose Non-Fermenting (SWI/SNF) chromatin remodeling complex and plays an important role in regulating tumor occurrence and development. Thus, it is of fundamental clinical importance to understand its molecular functions. However, there is limited research regarding its role in ovarian cancer. In this study, we report a key function of ARID1A in regulating Hh signaling pathway. We find that overexpression of ARID1A significantly inhibits cell proliferation and migration, these biological characteristics are enhanced in the ovarian cancer cells in which the ARID1A gene is knocked down. Mechanistically, overexpression of ARID1A downregulates posttranslational modification and activity of Shh ligand through inhibiting cholesterol synthesis. We further demonstrate that overexpression of ARID1A inhibits the expression of downstream molecule Gli1 in the Hh signaling pathway, whereas deficiency of ARID1A promotes Gli1 expression levels. Thus, the findings of this study demonstrate the critical role that ARID1A plays in the regulation of Hedgehog signaling pathway during ovarian cancer cell growth and migration, which may provide potential targets for the treatment of ovarian cancer.
Keywords: ARID1A, Hedgehog pathway, cholesterol, ovarian cancer.
Audience Take Away:
- This study provides new insights to design relevant therapeutic strategies for the treatment of ovarian cancer.
- Here, a new mechanism for the regulation of Hh signaling in this study is proposed, which is of great significance for the physiological and pathological research of tissues and organs.
- We explore the upstream regulatory molecules of Hh signaling and propose a new perspective on ARID1A regulating posttranslational modifications of Shh ligand.
