Yang Zhou1, Zhijun Jin2, Chengcai Wang3. 1. Department of Gynecology and Obstetrics, Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Gynecological Minimally Invasive Surgery Research Center, Tongji University School of Medicine, Shanghai 200072, China. 2. Department of Gynaecology and Obstetrics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. 3. Department of Anesthesia, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: wangchengcai81@sina.com.
Abstract
BACKGROUND: Ovarian cancer is one of the most common gynecologic cancers with high morbidity and mortality in women. Glycogen metabolism plays a critical role in cancer development and glycogen phosphorylase B (PYGB) has reported to be involved in various tumors. Here, we explored the role of PYGB in ovarian cancer. METHODS: PYGB mRNA expression were examined in ovarian cancer tissue and also analyzed using the dataset from The Cancer Genome Atlas cohort. Correlations between PYGB expression and prognosis of ovarian cancer patients were analyzed. PYGB was silenced to evaluate the ovarian cell proliferation, invasion and migration in vitro and tumorigenesis in vivo. MiR-133a-3p targeting PYGB was identified using online tools and confirmed with luciferase reporter experiment. MiR-133a-3p overexpression using miRNA mimics was conducted to evaluate its function on ovarian cancer cells. RESULTS: We showed that PYGB was upregulated in ovarian cancer tissue and high level of PYGB expression is markedly correlated with poor prognosis of ovarian cancer patients. PYGB knockdown significantly suppressed ovarian cancer cell proliferation, invasion and migration. Xenograft tumor formation further demonstrated that knockdown PYGB inhibited ovarian tumor development. Bioinformatics analysis revealed that PYGB regulated Wnt/β-catenin signaling pathway in ovarian cancer cells. Mechanistically, miR-133a-3p directly bound to 3'-untranslated region of PYGB and overexpression miR-133a-3p suppressed proliferation, invasion and migration in ovarian cancer cells. CONCLUSION: Our data suggest that miR-133a-3p/PYGB/Wnt-β-catenin axis plays a critical role in human ovarian cancer, which might serve as a promising therapeutic target of ovarian cancer treatment in the future.
BACKGROUND:Ovarian cancer is one of the most common gynecologic cancers with high morbidity and mortality in women. Glycogen metabolism plays a critical role in cancer development and glycogen phosphorylase B (PYGB) has reported to be involved in various tumors. Here, we explored the role of PYGB in ovarian cancer. METHODS:PYGB mRNA expression were examined in ovarian cancer tissue and also analyzed using the dataset from The Cancer Genome Atlas cohort. Correlations between PYGB expression and prognosis of ovarian cancerpatients were analyzed. PYGB was silenced to evaluate the ovarian cell proliferation, invasion and migration in vitro and tumorigenesis in vivo. MiR-133a-3p targeting PYGB was identified using online tools and confirmed with luciferase reporter experiment. MiR-133a-3p overexpression using miRNA mimics was conducted to evaluate its function on ovarian cancer cells. RESULTS: We showed that PYGB was upregulated in ovarian cancer tissue and high level of PYGB expression is markedly correlated with poor prognosis of ovarian cancerpatients. PYGB knockdown significantly suppressed ovarian cancer cell proliferation, invasion and migration. Xenograft tumor formation further demonstrated that knockdown PYGB inhibited ovarian tumor development. Bioinformatics analysis revealed that PYGB regulated Wnt/β-catenin signaling pathway in ovarian cancer cells. Mechanistically, miR-133a-3p directly bound to 3'-untranslated region of PYGB and overexpression miR-133a-3p suppressed proliferation, invasion and migration in ovarian cancer cells. CONCLUSION: Our data suggest that miR-133a-3p/PYGB/Wnt-β-catenin axis plays a critical role in humanovarian cancer, which might serve as a promising therapeutic target of ovarian cancer treatment in the future.
Authors: Christos E Zois; Anne M Hendriks; Syed Haider; Elisabete Pires; Esther Bridges; Dimitra Kalamida; Dimitrios Voukantsis; B Christoffer Lagerholm; Rudolf S N Fehrmann; Wilfred F A den Dunnen; Andrei I Tarasov; Otto Baba; John Morris; Francesca M Buffa; James S O McCullagh; Mathilde Jalving; Adrian L Harris Journal: Cell Death Dis Date: 2022-06-28 Impact factor: 9.685