Blood Serum From Head and Neck Squamous Cell Carcinoma Patients Induces Altered MicroRNA and Target Gene Expression Profile in Treated Cells

被引:16
作者
Allen, Brittany [1 ]
Schneider, Augusto [2 ]
Victoria, Berta [1 ]
Lopez, Yury O. Nunez [3 ]
Muller, Mark [4 ]
Szewczyk, Mateusz [5 ]
Pazdrowski, Jakub [5 ]
Majchrzak, Ewa [5 ]
Barczak, Wojciech [5 ]
Golusinski, Wojciech [5 ]
Golusinski, Pawel [5 ,6 ]
Masternak, Michal M. [1 ,5 ]
机构
[1] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA
[2] Univ Fed Pelotas, Fac Nutr, Pelotas, Brazil
[3] Florida Hosp, Translat Res Inst Metab & Diabet, Orlando, FL USA
[4] TopoGEN Inc, Epigenet Div, Buena Vista, CO USA
[5] Poznan Univ Med Sci, Greater Poland Canc Ctr, Dept Head & Neck Surg, Poznan, Poland
[6] Poznan Univ Med Sci, Head & Neck Canc Biol Lab, Biol & Environm Studies, Poznan, Poland
关键词
head and neck squamous cell carcinomas; microRNA; sequencing data analysis; p53; pathway; cancer-associated factors; HUMAN CANCER; LUNG-CANCER; MALIGNANT TRAIT; STEM-CELLS; MICROVESICLES; EXOSOMES; RNA; EPIDEMIOLOGY; BIOGENESIS; DIAGNOSIS;
D O I
10.3389/fonc.2018.00217
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The head and neck squamous cell carcinoma (HNSCC) represents one of the most common cancers in humans. Close to 600,000 new diagnoses are made every year worldwide and over half of diagnosed patients will not survive. In view of this low survival rate, the development of novel cell-based assays for HNSCC will allow more mechanistic approaches for specific diagnostics for each individual patient. The cell-based assays will provide more informative data predicting cellular processes in treated patient, which in effect would improve patient follow up. More importantly, it will increase the specificity and effectiveness of therapeutic approaches. In this study, we investigated the role of serum from HNSCC patients on the regulation of microRNA (miRNA) expression in exposed cells in vitro. Next-generation sequencing of miRNA revealed that serum from HNSCC patients induced a different miRNA expression profile than the serum from healthy individuals. Out of 377 miRNA detected, we found that 16 miRNAs were differentially expressed when comparing cells exposed to serum from HNSCC or healthy individuals. The analysis of gene ontologies and pathway analysis revealed that these miRNA target genes were involved in biological cancer-related processes, including cell cycle and apoptosis. The real-time PCR analysis revealed that serum from HNSCC patients downregulate the expression level of five genes involved in carcinogenesis and two of these genes-P53 and SLC2A1-are direct targets of detected miRNAs. These novel findings provide new insight into how cancer-associated factors in circulation regulate the expression of genes and regulatory elements in distal cells in favor of tumorigenesis. This has the potential for new therapeutic approaches and more specific diagnostics with tumor-specific cell lines or single-cell in vitro assays for personalized treatment and early detection of primary tumors or metastasis.
引用
收藏
页数:9
相关论文
共 59 条
[1]
Neoplastic Reprogramming of Patient-Derived Adipose Stem Cells by Prostate Cancer Cell-Associated Exosomes [J].
Abd Elmageed, Zakaria Y. ;
Yang, Yijun ;
Thomas, Raju ;
Ranjan, Manish ;
Mondal, Debasis ;
Moroz, Krzysztof ;
Fang, Zhide ;
Rezk, Bashir M. ;
Moparty, Krishnarao ;
Sikka, Suresh C. ;
Sartor, Oliver ;
Abdel-Mageed, Asim B. .
STEM CELLS, 2014, 32 (04) :983-997
[2]
Transfer of malignant trait to immortalized human cells following exposure to human cancer serum [J].
Abdouh, Mohamed ;
Zhou, Shufeng ;
Arena, Vincenzo ;
Arena, Manuel ;
Lazaris, Anthoula ;
Onerheim, Ronald ;
Metrakos, Peter ;
Arena, Goffredo Orazio .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2014, 33
[3]
Differential expression analysis for sequence count data [J].
Anders, Simon ;
Huber, Wolfgang .
GENOME BIOLOGY, 2010, 11 (10)
[4]
Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences [J].
Balaj, Leonora ;
Lessard, Ryan ;
Dai, Lixin ;
Cho, Yoon-Jae ;
Pomeroy, Scott L. ;
Breakefield, Xandra O. ;
Skog, Johan .
NATURE COMMUNICATIONS, 2011, 2
[5]
MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[6]
INDUCTION OF APOPTOSIS BY TUMOR-SUPPRESSOR GENES AND ONCOGENES [J].
CANMAN, CE ;
KASTAN, MB .
SEMINARS IN CANCER BIOLOGY, 1995, 6 (01) :17-25
[7]
miR-15 and miR-16 induce apoptosis by targeting BCL2 [J].
Cimmino, A ;
Calin, GA ;
Fabbri, M ;
Iorio, MV ;
Ferracin, M ;
Shimizu, M ;
Wojcik, SE ;
Aqeilan, RI ;
Zupo, S ;
Dono, M ;
Rassenti, L ;
Alder, H ;
Volinia, S ;
Liu, CG ;
Kipps, TJ ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (39) :13944-13949
[8]
MicroRNAs and endocrine biology [J].
Cuellar, TL ;
McManus, MT .
JOURNAL OF ENDOCRINOLOGY, 2005, 187 (03) :327-332
[9]
Denaro N, 2011, ISRN Otolaryngol, V2011, P931813, DOI 10.5402/2011/931813
[10]
MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B [J].
Fabbri, Muller ;
Garzon, Ramiro ;
Cimmino, Amelia ;
Liu, Zhongfa ;
Zanesi, Nicola ;
Callegari, Elisa ;
Liu, Shujun ;
Alder, Hansjuerg ;
Costinean, Stefan ;
Fernandez-Cymering, Cecilia ;
Volinia, Stefano ;
Guler, Gulnur ;
Morrison, Carl D. ;
Chan, Kenneth K. ;
Marcucci, Guido ;
Calin, George A. ;
Huebner, Kay ;
Croce, Carlo M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (40) :15805-15810