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.
Highlights
Ovarian cancer is one of the most lethal gynecologic cancers causing around 13,940 deaths in 2020 (American Cancer Society), which accounts for 5% cancer deaths among women [1,2]
The subsequent studies have reported that CCAT2 is positively associated with distant metastasis of non-small cell lung cancer [9], breast cancer [10,11], ovarian cancer [1,12,13], cervical cancer [14,15] and gastric cancer [16,17], which suggests that CCAT2 could be a prognostic biomarker for tumor metastasis
Using chromatin immunoprecipitation (ChIP) assay, we found that in both SKOV3 and A2780 cells, siRNA knockdown of CCAT2 or calcitriol treatment caused a decrease in the binding of TCF4 to the MYC promoter (Figure 6C)
Summary
Ovarian cancer is one of the most lethal gynecologic cancers causing around 13,940 deaths in 2020 (American Cancer Society), which accounts for 5% cancer deaths among women [1,2]. Over 70% of ovarian cancer patients are diagnosed in advanced stages (III and IV) with less than 30% five-year survival rates [1,3,4]. Such poor clinical outcomes are mainly caused by late diagnosis and cancer resistance to chemotherapy, which leads to disease progression with highly aggressive metastasis [5]. We examined the effect of calcitriol on ovarian cancer cell proliferation. All experiments have been repeated three times and data shown are mean values ± SD, (*) p < 0.05; (**) p < 0.01; (***) p < 0.001
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
