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SNORD89 promotes stemness phenotype of ovarian cancer cells by regulating Notch1-c-Myc pathway

文献类型：期刊论文

作者Zhu, Wenjing1,2; Niu, Jumin3; He, Miao1,4; Zhang, Liwen1,4; Lv, Xuemei1,4; Liu, Fangxiao1,4; Jiang, Longyang1,4; Zhang, Jing1,4; Yu, Zhaojin1,4; Zhao, Lin1,4
刊名JOURNAL OF TRANSLATIONAL MEDICINE
出版日期2019-08-08
卷号17期号:1页码:15
关键词Ovarian cancer stem cells TCGA SNORNAs SNORD89
DOI10.1186/s12967-019-2005-1
通讯作者Ding, Jian(jding@simm.ac.cn) ; Wei, Minjie(weiminjiecmu@163.com)
英文摘要Background Ovarian cancer is the leading cause of death in gynecological cancer. Cancer stem cells (CSCs) contribute to the occurrence, progression and resistance. Small nucleolar RNAs (SnoRNAs), a class of small molecule non-coding RNA, involve in the cancer cell stemness and tumorigenesis. Methods In this study, we screened out SNORNAs related to ovarian patient's prognosis by analyzing the data of 379 cases of ovarian cancer patients in the TCGA database, and analyzed the difference of SNORNAs expression between OVCAR-3 (OV) sphere-forming (OS) cells and OV cells. After overexpression or knockdown SNORD89, the expression of Nanog, CD44, and CD133 was measured by qRT-PCR or flow cytometry analysis in OV, CAOV-3 (CA) and OS cells, respectively. CCK-8 assays, plate clone formation assay and soft agar colony formation assay were carried out to evaluate the changes of cell proliferation and self-renewal ability. Scratch migration assay and trans-well invasion analysis were used for assessing the changes of migration and invasion ability. Results High expression of SNORD89 indicates the poor prognosis of ovarian cancer patients and was associated with patients' age, therapy outcome. SNORD89 highly expressed in ovarian cancer stem cells. The overexpression of SNORD89 resulted in the increased stemness markers, S phase cell cycle, cell proliferation, invasion and migration ability in OV and CA cells. Conversely, these phenomena were reversed after SNORD89 silencing in OS cells. Further, we found that SNORD89 could upregulate c-Myc and Notch1 expression in mRNA and protein levels. SNORD89 deteriorates the prognosis of ovarian cancer patients by regulating Notch1-c-Myc pathway to promote cell stemness and acts as an oncogene in ovarian tumorigenesis. Consequently, SNORD89 can be a novel prognostic biomarker and therapeutic target for ovarian cancer.
WOS关键词SMALL NUCLEOLAR RNA ; SELF-RENEWAL ; C-MYC ; EXPRESSION ; RESISTANCE ; TUMORIGENESIS ; GENERATION ; CARCINOMA ; DIAGNOSIS ; INVASION
资助项目National Natural Science Foundation of China[81572898] ; National Natural Science Foundation of China[81673475] ; National Natural Science Foundation of China[81502996] ; National Natural Science Foundation of China[81601370] ; National Natural Science Foundation of China and Liaoning joint fund key program[U1608281] ; Drug Innovation Major Project[2018ZX09711001-008-006] ; Key Laboratory Foundation from Shenyang ST Projects[Z18-4-020] ; Liaoning Province Scientific Research Foundation[20180550500] ; Liaoning Province Scientific Research Foundation[LQNK20173] ; Liaoning Province Scientific Research Foundation[20170541024]
WOS研究方向Research & Experimental Medicine
语种英语
出版者BMC
WOS记录号WOS:000480478900002
源URL[http://119.78.100.183/handle/2S10ELR8/288914]  
专题新药研究国家重点实验室
通讯作者Ding, Jian; Wei, Minjie
作者单位1.China Med Univ, Sch Pharm, Dept Pharmacol, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China
2.Qingdao Municipal Hosp, Dept Pharm, Qingdao, Shandong, Peoples R China
3.Shenyang Womens & Childrens Hosp, Shenyang, Liaoning, Peoples R China
4.China Med Univ, Liaoning Engn Technol Res Ctr Res Dev & Industria, Shenyang, Liaoning, Peoples R China
5.China Med Univ, Sch Pharm, Dept Pharmaceut, Shenyang, Liaoning, Peoples R China
6.Natl Univ Singapore, Bioinformat & Drug Design Grp, Dept Pharm, 18 Sci Dr 4, Singapore 117543, Singapore
7.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Wenjing,Niu, Jumin,He, Miao,et al. SNORD89 promotes stemness phenotype of ovarian cancer cells by regulating Notch1-c-Myc pathway[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2019,17(1):15.
APA Zhu, Wenjing.,Niu, Jumin.,He, Miao.,Zhang, Liwen.,Lv, Xuemei.,...&Wei, Minjie.(2019).SNORD89 promotes stemness phenotype of ovarian cancer cells by regulating Notch1-c-Myc pathway.JOURNAL OF TRANSLATIONAL MEDICINE,17(1),15.
MLA Zhu, Wenjing,et al."SNORD89 promotes stemness phenotype of ovarian cancer cells by regulating Notch1-c-Myc pathway".JOURNAL OF TRANSLATIONAL MEDICINE 17.1(2019):15.

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来源：上海药物研究所

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