Hsa_circ_0014717 is downregulated in colorectal cancer and inhibits tumor growth by promoting p16 expression

被引:60
作者
Wang, Feng [1 ]
Wang, Jun [2 ]
Cao, Xiangyu [3 ]
Xu, Lihui [3 ]
Chen, Lin [4 ]
机构
[1] Nantong Univ, Affiliated Hosp, Dept Clin Lab, Nantong 226001, Jiangsu, Peoples R China
[2] Nanjing Univ, Affiliated Drum Tower Hosp, Dept Gen Surg, Nanjing 210008, Jiangsu, Peoples R China
[3] Nantong Univ, Xinglin Coll, Clin Med, Nantong 226008, Jiangsu, Peoples R China
[4] Nantong Univ, Nantong Hosp 3, Dept Gastroenterol & Clin Lab, Nantong 226006, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Circular RNA; Hsa_circ_0014717; Colorectal cancer p16; Cell proliferation; Cell cycle; CIRCULAR RNAS BIOGENESIS; P16(INK4A); SENESCENCE; CARCINOMA; PROFILE; ROLES;
D O I
10.1016/j.biopha.2018.01.015
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that may regulate gene expression in eukaryotes. Nevertheless, their potential functions in human malignancies are still largely unknown. The aim of this study was to explore the expression of hsa_circ_0014717 in colorectal cancer (CRC) and its role involving in tumor growth. We found that hsa_circ_0014717 was downregulated in CRC tissues and cell lines, and was significantly correlated with TNM stage, distal metastasis and poor overall survival of CRC patients as well. Moreover, our gain-of-function analysis further showed that hsa_circ_0014717 overexpression could significantly suppress CRC cell proliferation and colony formation, as well as induce cell cycle G0/G1 phase arrest in vitro and inhibit xenograft tumor growth in vivo. In addition, hsa_circ_0014717 could upregulate the expression of cell cycle inhibitory protein p16. Besides, p16 knockdown could reverse hsa_circ_0014717 mediated growth inhibition of CRC cells. Taken together, hsa_circ_0014717 acts as a potential tumor suppressor that inhibits CRC growth, partly at least, through upregulating p16 expression. Furthermore, our present study may provide a promising therapeutic target for CRC patients.
引用
收藏
页码:775 / 782
页数:8
相关论文
共 32 条
[1]   Biogenesis, identification, and function of exonic circular RNAs [J].
Chen, Iju ;
Chen, Chia-Ying ;
Chuang, Trees-Juen .
WILEY INTERDISCIPLINARY REVIEWS-RNA, 2015, 6 (05) :563-579
[2]   Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer [J].
Chen, Jie ;
Li, Yan ;
Zheng, Qiupeng ;
Bao, Chunyang ;
He, Jian ;
Chen, Bin ;
Lyu, Dongbin ;
Zheng, Biqiang ;
Xu, Yu ;
Long, Ziwen ;
Zhou, Ye ;
Zhu, Huiyan ;
Wang, Yanong ;
He, Xianghuo ;
Shi, Yingqiang ;
Huang, Shenglin .
CANCER LETTERS, 2017, 388 :208-219
[3]   Circular RNAs: a new frontier in the study of human diseases [J].
Chen, Yonghua ;
Li, Cheng ;
Tan, Chunlu ;
Liu, Xubao .
JOURNAL OF MEDICAL GENETICS, 2016, 53 (06) :359-365
[4]   Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells [J].
Diep, Caroline H. ;
Charles, Nathan J. ;
Gilks, C. Blake ;
Kalloger, Steve E. ;
Argenta, Peter A. ;
Lange, Carol A. .
CELL CYCLE, 2013, 12 (09) :1433-1449
[5]   Circular RNAs: Biogenesis, Function and Role in Human Diseases [J].
Greene, John ;
Baird, Anne-Marie ;
Brady, Lauren ;
Lim, Marvin ;
Gray, Steven G. ;
McDermott, Raymond ;
Finn, Stephen P. .
FRONTIERS IN MOLECULAR BIOSCIENCES, 2017, 4
[6]   Circular RNA circMTO1 Acts as the Sponge of MicroRNA-9 to Suppress Hepatocellular Carcinoma Progression [J].
Han, Dan ;
Li, Jiangxue ;
Wang, Huamin ;
Su, Xiaoping ;
Hou, Jin ;
Gu, Yan ;
Qian, Cheng ;
Lin, Yun ;
Liu, Xiang ;
Huang, Mingyan ;
Li, Nan ;
Zhou, Weiping ;
Yu, Yizhi ;
Cao, Xuetao .
HEPATOLOGY, 2017, 66 (04) :1151-1164
[7]   Noncoding Effects of Circular RNA CCDC66 Promote Colon Cancer Growth and Metastasis [J].
Hsiao, Kuei-Yang ;
Lin, Ya-Chi ;
Gupta, Sachin Kumar ;
Chang, Ning ;
Yen, Laising ;
Sun, H. Sunny ;
Tsai, Shaw-Jenq .
CANCER RESEARCH, 2017, 77 (09) :2339-2350
[8]   Circular RNAs in colorectal cancer: Possible roles in regulation of cancer cells [J].
Isabel Taborda, Maria ;
Ramirez, Sebastian ;
Bernal, Giuliano .
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2017, 9 (02) :62-69
[9]  
Jemal A, 2011, CA-CANCER J CLIN, V61, P134, DOI [10.3322/caac.21492, 10.3322/caac.20115, 10.3322/caac.20107]
[10]   Circular RNAs are miRNA sponges and can be used as a new class of biomarker [J].
Kulcheski, Franceli Rodrigues ;
Christoff, Ana Paula ;
Margis, Rogerio .
JOURNAL OF BIOTECHNOLOGY, 2016, 238 :42-51