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Published on: January 12, 2020
Vitamin D Suppresses Ovarian Cancer Growth and Invasion by Targeting Long Non-Coding RNA CCAT2
Liye Wang1, Shuang Zhou1, Bin Guo1
1Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
Abstract:
Ovarian cancer is the most deadly gynecologic cancer among women worldwide. Poor response to current treatment makes it necessary to discover new diagnostic biomarkers to detect the cancer early and develop new and effective prevention strategies. Calcitriol, the active metabolite of vitamin D, protects against multiple cancers through unelucidated mechanisms. The oncogenic long non-coding RNA (lncRNA) CCAT2 (colon cancer associated transcript 2) is overexpressed in ovarian cancer. Here, we foundd that calcitriol inhibited CCAT2 expression in ovarian cancer cell lines. Treatment with calcitriol inhibited ovarian cancer cell proliferation, migration, and invasion. As a result of CCAT2 inhibition, calcitriol decreased the binding of transcription factor TCF7L2 (TCF4) to the MYC promoter, resulting in the repression of c-Myc protein expression. Our results suggest a novel anti-cancer mechanism of vitamin D by targeting CCAT2 in ovarian cancer. The findings may help develop vitamin D as a practical and inexpensive nutraceutical for ovarian cancer prevention.
Insights
Vitamin D
Area of Science:
- Oncology
- Molecular Biology
- Nutraceuticals
Background:
- Ovarian cancer is a leading cause of cancer death in women globally.
- Current treatments for ovarian cancer have limited efficacy, necessitating new biomarkers and prevention strategies.
- Calcitriol, the active form of vitamin D, exhibits anti-cancer properties via unknown mechanisms.
Purpose of the Study:
- To investigate the role of calcitriol in ovarian cancer.
- To explore the effect of calcitriol on the long non-coding RNA CCAT2 (colon cancer associated transcript 2) in ovarian cancer.
- To elucidate the anti-cancer mechanism of vitamin D in ovarian cancer.
Main Methods:
- Ovarian cancer cell lines were treated with calcitriol.
- CCAT2 expression levels were measured.
- Cell proliferation, migration, and invasion assays were performed.
- The binding of transcription factor TCF7L2 (TCF4) to the MYC promoter and c-Myc protein expression were analyzed.
Main Results:
- Calcitriol significantly inhibited CCAT2 expression in ovarian cancer cells.
- Calcitriol treatment reduced ovarian cancer cell proliferation, migration, and invasion.
- Calcitriol decreased TCF7L2 binding to the MYC promoter, leading to reduced c-Myc protein expression.
- These effects were linked to the inhibition of CCAT2 by calcitriol.
Conclusions:
- Calcitriol demonstrates a novel anti-cancer mechanism in ovarian cancer by targeting CCAT2.
- Vitamin D may serve as a potential nutraceutical for ovarian cancer prevention.
- Targeting CCAT2 offers a new therapeutic strategy for ovarian cancer.
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