机构:[1]Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai 200086[2]Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine[3]Longhua hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031[4]College of Pharmacy, Chongqing Medical University, Chongqing, Sichuan 400016[5]Shanghai Topbiox Co., Ltd.[6]Shanghai Geriatric Institute of Chinese Medicine,Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China
Angiogenesis has an important role in tumour cell growth and metastasis. Anisomycin has been shown to inhibit tumour cell growth. However, whether anisomycin can inhibit angiogenesis of tumours has not been reported. The present study demonstrated that there was a positive correlation between tumour angiogenesis and the number of CD44+/CD133+ serous human ovarian cancer stem cells (HuOCSCs). Subsequently, it was confirmed that anisomycin significantly inhibited the proliferation, invasion, tumorigenic ability and tumour angiogenesis of HuOCSCs. Gene expression profiling by cDNA microarrays revealed that the expression levels of vascular endothelial cell markers, platelet‑derived growth factors, Notch pathway components and 27 tumour angiogenesis‑related genes were significantly decreased in the anisomycin‑treated group compared with the control group. Further experiments demonstrated that the expression levels of endogenous long non‑coding RNA (lncRNA) maternally expressed 3 (Meg3) were significantly decreased in anisomycin‑treated HuOCSCs, whereas the expression levels of microRNA (miR)‑421 were significantly increased. The results of luciferase reporter assays indicated that, when miR‑421 was overexpressed in cells, the luciferase activities of wild‑type platelet derived growth factor receptor α (PDGFRA) 3' untranslated region and Meg3 reporter plasmids were significantly decreased. Overexpression of miR‑421 in HuOCSCs significantly enhanced the anisomycin‑mediated inhibition of HuOCSC proliferation. Taken together, the present results demonstrated that anisomycin inhibited the activation downstream of the Notch1 pathway by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis, ultimately inhibiting angiogenesis, proliferation and invasion in ovarian cancer cells.
基金:
Shanghai Natural Science Foundation (grant no. 16ZR1434000), the Development Fund for Shanghai Talents (grant no. 2017054), the Fund for Xinglin Talents of Shanghai University of Traditional Chinese Medicine (grant no. 201707081) and the National Natural Science Foundation of China (grant no. 81973899).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2019]版:
大类|3 区医学
小类|3 区肿瘤学
最新[2023]版:
大类|3 区医学
小类|3 区肿瘤学
第一作者:
第一作者机构:[1]Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai 200086
共同第一作者:
通讯作者:
通讯机构:[6]Shanghai Geriatric Institute of Chinese Medicine,Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China[*1]Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China
推荐引用方式(GB/T 7714):
Ye Weiping,Ni Zhentian,Yicheng Shen,et al.Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis.[J].International journal of oncology.2019,55(6):1296-1312.doi:10.3892/ijo.2019.4887.
APA:
Ye Weiping,Ni Zhentian,Yicheng Shen,Pan Hao,Huang Yongyi...&Liu Te.(2019).Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis..International journal of oncology,55,(6)
MLA:
Ye Weiping,et al."Anisomycin inhibits angiogenesis in ovarian cancer by attenuating the molecular sponge effect of the lncRNA‑Meg3/miR‑421/PDGFRA axis.".International journal of oncology 55..6(2019):1296-1312