MicroRNA-299-5p inhibits cell metastasis in breast cancer by directly targeting serine/threonine kinase 39

被引:27
作者
Li, Chenxing [1 ]
Wang, Aiying [1 ]
Chen, Yanke [1 ]
Liu, Yan [2 ]
Zhang, Hui [3 ]
Zhou, Jun [4 ]
机构
[1] Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Genet & Cell Biol, Hlth Sci Ctr, Xian 710061, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Dept Prevent Dent, Coll Stomatol, Clin Res Ctr Shaanxi Prov Dent & Maxillofacial Di, Xian 710004, Shaanxi, Peoples R China
[3] Xi An Jiao Tong Univ, Coll Pharm, Hlth Sci Ctr, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China
[4] Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Pharmacol, Hlth Sci Ctr, 76 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China
关键词
miR-299-5p; serine; threonine kinase 39; breast cancer; migration; invasion; microRNA; MESENCHYMAL TRANSITION; PROTEIN-KINASES; EXPRESSION; PROGNOSIS; INVASION; STK39; SPAK; PROLIFERATION; BIOMARKERS; MIGRATION;
D O I
10.3892/or.2020.7486
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Numerous studies have demonstrated that microRNAs (miRNAs) play a key role in human carcinogenesis and metastasis. For example, miR-299-5p has previously been revealed to be dysregulated in several human cancers. However, the biological function of miR-299-5p in breast cancer remains unclear. The present study demonstrated that miR-299-5p was downregulated in breast cancer tissues and cell lines. The restoration of miR-299-5p expression suppressed cell migration and invasion, whereas inhibition of miR-299-5p promoted cell migration and invasion. In addition, in vivo studies demonstrated that miR-299-5p overexpression was able to inhibit tumour metastasis in nude mice. Mechanistically, through bioinformatics analysis and a dual-luciferase assay, it was confirmed that miR-299-5p directly targets serine/threonine kinase 39 (STK39). Silencing STK39 inhibited cell metastasis and suppressed epithelial-mesenchymal transition markers and matrix metalloproteinase expression, whereas restoration of STK39 expression was able to reverse miR-299-5p-inhibited cell migration and invasion. Collectively, the results of the present study demonstrated that miR-299-5p supresses breast cancer cell migration and invasion by targeting STK39. These findings may provide novel insights into miR-299-5p and its potential diagnostic and therapeutic benefits in breast cancer.
引用
收藏
页码:1221 / 1233
页数:13
相关论文
共 41 条
[1]   The WNK-SPAK/OSR1 pathway: Master regulator of cation-chloride cotransporters [J].
Alessi, Dario R. ;
Zhang, Jinwei ;
Khanna, Arjun ;
Hochdoerfer, Thomas ;
Shang, Yuze ;
Kahle, Kristopher T. .
SCIENCE SIGNALING, 2014, 7 (334)
[2]   The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis [J].
Benetatos, Leonidas ;
Hatzimichael, Eleftheria ;
Londin, Eric ;
Vartholomatos, George ;
Loher, Phillipe ;
Rigoutsos, Isidore ;
Briasoulis, Evangelos .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2013, 70 (05) :795-814
[3]   MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer [J].
Bertoli, Gloria ;
Cava, Claudia ;
Castiglioni, Isabella .
THERANOSTICS, 2015, 5 (10) :1122-1143
[4]   MicroRNA-519a-3p mediates apoptosis resistance in breast cancer cells and their escape from recognition by natural killer cells [J].
Breunig, Christian ;
Pahl, Jens ;
Kueblbeck, Moritz ;
Miller, Matthias ;
Antonelli, Daniela ;
Erdem, Nese ;
Wirth, Cornelia ;
Will, Rainer ;
Bott, Alexander ;
Cerwenka, Adelheid ;
Wiemann, Stefan .
CELL DEATH & DISEASE, 2017, 8 :e2973-e2973
[5]   3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3) [J].
Cardoso, F. ;
Costa, A. ;
Senkus, E. ;
Aapro, M. ;
Andre, F. ;
Barrios, C. H. ;
Bergh, J. ;
Bhattacharyya, G. ;
Biganzoli, L. ;
Cardoso, M. J. ;
Carey, L. ;
Corneliussen-James, D. ;
Curigliano, G. ;
Dieras, V. ;
El Saghir, N. ;
Eniu, A. ;
Fallowfield, L. ;
Fenech, D. ;
Francis, P. ;
Gelmon, K. ;
Gennari, A. ;
Harbeck, N. ;
Hudis, C. ;
Kaufman, B. ;
Krop, I. ;
Mayer, M. ;
Meijer, H. ;
Mertz, S. ;
Ohno, S. ;
Pagani, O. ;
Papadopoulos, E. ;
Peccatori, F. ;
Penault-Llorca, F. ;
Piccart, M. J. ;
Pierga, J. Y. ;
Rugo, H. ;
Shockney, L. ;
Sledge, G. ;
Swain, S. ;
Thomssen, C. ;
Tutt, A. ;
Vorobiof, D. ;
Xu, B. ;
Norton, L. ;
Winer, E. .
ANNALS OF ONCOLOGY, 2017, 28 (01) :16-33
[6]   EMT, cell plasticity and metastasis [J].
Chaffer, Christine L. ;
San Juan, Beatriz P. ;
Lim, Elgene ;
Weinberg, Robert A. .
CANCER AND METASTASIS REVIEWS, 2016, 35 (04) :645-654
[7]   Suppression of SPIN1-mediated PI3K-Akt pathway by miR-489 increases chemosensitivity in breast cancer [J].
Chen, Xu ;
Wang, Ya-Wen ;
Xing, Ai-Yan ;
Xiang, Shuai ;
Shi, Duan-Bo ;
Liu, Lei ;
Li, Yan-Xiang ;
Gao, Peng .
JOURNAL OF PATHOLOGY, 2016, 239 (04) :459-472
[8]   SPAK and OSR1: STE20 kinases involved in the regulation of ion homoeostasis and volume control in mammalian cells [J].
Delpire, Eric ;
Gagnon, Kenneth B. E. .
BIOCHEMICAL JOURNAL, 2008, 409 (02) :321-331
[9]   Osteopontin promotes epithelial-mesenchymal transition of hepatocellular carcinoma through regulating vimentin [J].
Dong, Qiongzhu ;
Zhu, Xuchao ;
Dai, Chun ;
Zhang, Xiaofei ;
Gao, Xiaomei ;
Wei, Jinwang ;
Sheng, Yuanyuan ;
Zheng, Yan ;
Yu, Jian ;
Xie, Lu ;
Qin, Yi ;
Qiao, Peng ;
Zhou, Chuang ;
Yu, Xinxin ;
Jia, Huliang ;
Ren, Ning ;
Zhou, Haijun ;
Ye, Qinghai ;
Qin, Lunxiu .
ONCOTARGET, 2016, 7 (11) :12997-13012
[10]   MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells [J].
Formosa, A. ;
Markert, E. K. ;
Lena, A. M. ;
Italiano, D. ;
Finazzi-Agro, E. ;
Levine, A. J. ;
Bernardini, S. ;
Garabadgiu, A. V. ;
Melino, G. ;
Candi, E. .
ONCOGENE, 2014, 33 (44) :5173-5182