MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal cancer

被引:38
作者
Gao, S. [1 ,2 ]
Liu, H. [1 ,2 ]
Hou, S. [1 ,2 ]
Wu, L. [3 ,4 ,5 ]
Yang, Z. [3 ,4 ,5 ]
Shen, J. [6 ]
Zhou, L. [3 ,4 ,5 ]
Zheng, S. -S. [3 ,4 ,5 ]
Jiang, B. [1 ,2 ]
机构
[1] Third Peoples Hosp Shanxi Prov, Shanxi Canc Hosp & Inst, Dept Colorectal Canc, 3 Xinchun Rd, Taiyuan 030013, Shanxi, Peoples R China
[2] Shanxi Med Univ, Affiliated Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China
[3] Minist Publ Hlth, Key Lab Combined Multiorgan Transplantat, Hangzhou 310003, Zhejiang, Peoples R China
[4] Key Lab Organ Transplantat, Hangzhou 310003, Zhejiang, Peoples R China
[5] Zhejiang Univ, Affiliated Hosp 1, Div Hepatobiliary & Pancreat Surg, Dept Surg,Sch Med, Hangzhou 310003, Zhejiang, Peoples R China
[6] Licheng Cty Peoples Hosp, Dept Gen Surg, Licheng 647600, Peoples R China
关键词
Colorectal cancer; miR-489; HDAC7; Tumor invasion; METASTASIS; CARCINOMA; PATHWAY;
D O I
10.1007/s12094-017-1770-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose The expression of miR-489 is linked to tumor development and progression; nevertheless, its role in tumor growth and invasion of colorectal cancer (CRC) and the underlying mechanism has not been clarified. Experimental design We used quantitative RT-PCR to measure the expression of mature miR-489 in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were predicted with TargetScan and substantiated by dual-luciferase reporter assay. Furthermore, we did in vitro and in vivo analysis with expression vectors and small interfering RNAs, to elucidate the precise role of miR-489 and its target gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion. Results Compared to the corresponding non-tumor tissues, miR-489 was frequently downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC recurrence free survival years in the group with elevated miR-489 expression than those with lower miR-489 expression. In addition, we examined that miR-489 obviously inhibited the migratory and invasive capability in CRC. In further study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and downregulates its expression, and HDAC7 expression promoted tumor cell proliferation and invasion. We demonstrated that miR-489 suppresses tumor invasion and metastasis in CRC by targeting HDAC7. Conclusions We identified that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial light on how miR-489 functions in CRC pathogenesis.
引用
收藏
页码:703 / 712
页数:10
相关论文
共 17 条
[1]   Blood-based microRNAs as biomarkers for the diagnosis of colorectal cancer: a systematic review and meta-analysis [J].
Carter, Jane V. ;
Galbraith, Norman J. ;
Yang, Dongyan ;
Burton, James F. ;
Walker, Samuel P. ;
Galandiuk, Susan .
BRITISH JOURNAL OF CANCER, 2017, 116 (06) :762-774
[2]   Sustained expression of miR-26a promotes chromosomal instability and tumorigenesis through regulation of CHFR [J].
Castellano, Leandro ;
Dabrowska, Aleksandra ;
Pellegrino, Loredana ;
Ottaviani, Silvia ;
Cathcart, Paul ;
Frampton, Adam E. ;
Krell, Jonathan ;
Stebbing, Justin .
NUCLEIC ACIDS RESEARCH, 2017, 45 (08) :4401-4412
[3]  
Chitturi S, 2009, J GASTROEN HEPATOL, V24, P1
[4]   MicroRNA-466 inhibits tumor growth and bone metastasis in prostate cancer by direct regulation of osteogenic transcription factor RUNX2 [J].
Colden, Melissa ;
Dar, Altaf A. ;
Saini, Sharanjot ;
Dahiya, Priya V. ;
Shahryari, Varahram ;
Yamamura, Soichiro ;
Tanaka, Yuichiro ;
Stein, Gary ;
Dahiya, Rajvir ;
Majid, Shahana .
CELL DEATH & DISEASE, 2017, 8 :e2572-e2572
[5]   The molecular pathology of cancer [J].
Harris, Timothy J. R. ;
McCormick, Frank .
NATURE REVIEWS CLINICAL ONCOLOGY, 2010, 7 (05) :251-265
[6]   Hepatocellular carcinoma [J].
Hussain, SA ;
Ferry, DR ;
El-Gazzaz, G ;
Mirza, DF ;
James, ND ;
McMaster, P ;
Kerr, DJ .
ANNALS OF ONCOLOGY, 2001, 12 (02) :161-172
[7]   MiR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway [J].
Jiang, Li ;
He, Dongxu ;
Yang, Dantong ;
Chen, Zhen ;
Pan, Qiongxi ;
Mao, Aiqin ;
Cai, Yanfei ;
Li, Xiyuan ;
Xing, Hui ;
Shi, Mei ;
Chen, Yun ;
Bruce, Iain C. ;
Wang, Teng ;
Jin, Linfang ;
Qi, Xiaowei ;
Hua, Dong ;
Jin, Jian ;
Ma, Xin .
FEBS LETTERS, 2014, 588 (11) :2009-2015
[8]   miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC) [J].
Kikkawa, N. ;
Hanazawa, T. ;
Fujimura, L. ;
Nohata, N. ;
Suzuki, H. ;
Chazono, H. ;
Sakurai, D. ;
Horiguchi, S. ;
Okamoto, Y. ;
Seki, N. .
BRITISH JOURNAL OF CANCER, 2010, 103 (06) :877-884
[9]   The continuing challenge of hepatic cancer in Asia [J].
Lai, ECH ;
Lau, WY .
SURGEON-JOURNAL OF THE ROYAL COLLEGES OF SURGEONS OF EDINBURGH AND IRELAND, 2005, 3 (03) :210-215
[10]   CCL20/CCR6 promotes cell proliferation and metastasis in laryngeal cancer by activating p38 pathway [J].
Lu, Eryong ;
Su, Jili ;
Zhou, Yanhui ;
Zhang, Chao ;
Wang, Yuehui .
BIOMEDICINE & PHARMACOTHERAPY, 2017, 85 :486-492