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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00959

Profiling of tRNA halves and YRNA fragments in serum and tissue from oral squamous cell carcinoma patients identify key role of 5’ tRNA-Val-CAC-2-1 half

Joseph Dhahbi1*,  Yury Nunez-Lopez2,  Augusto Schneider3,  Berta Victoria3, Tatiana Saccon4, Krish Bharat5, Thaddeus McClatchey5, Hani Atamna1, Wojciech Scierski6,  Pawel Golusinski7,  Wojciech Golusiński7 and  Michal Masternak3*
  • 1California University of Science and Medicine, United States
  • 2Translational Research Institute for Metabolism and Diabetes (TRI), United States
  • 3Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, United States
  • 4Burnett School of Biomedical Sciences, University of Central Florida, United States
  • 5School of Medicine, California University of Science and Medicine, United States
  • 6Medical University of Silesia, Poland
  • 7Greater Poland Cancer Center, Poland

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer and, as indicated by The Oral Cancer Foundation, kills at an alarming rate of roughly one person per hour. With this study, we aimed at better understanding disease mechanisms and identifying minimally invasive disease biomarkers by profiling novel small noncoding RNAs (specifically, tRNA halves and YRNA fragments) in both serum and tumor tissue from humans. Small RNA-Sequencing identified multiple 5’ tRNA halves and 5’ YRNA fragments that displayed significant differential expression levels in circulation and/or tumor tissue, as compared to control counterparts. In addition, by implementing a modification of weighted gene coexpression network analysis, we identified an upregulated genetic module comprised of 5’ tRNA halves and miRNAs (miRNAs were described in previous study using the same samples) with significant association with the cancer trait. By consequently implementing miRNA-overtargeting network analysis, the biological function of the module (and by “guilt by association”, the function of the 5’ tRNA-Val-CAC-2-1 half) was found to involve the transcriptional targeting of specific genes involved in the negative regulation of the G1/S transition of the mitotic cell cycle. These findings suggest that 5’ tRNA-Val-CAC-2-1 half (reduced in serum of OSCC patients and elevated in the tumor tissue) could potentially serve as an OSCC circulating biomarker and/or target for novel anticancer therapies. To our knowledge, this is the first time that the specific molecular function of a 5’-tRNA half is specifically pinpointed in OSCC.

Keywords: 5’ tRNA halves, 5’ YRNA fragments, oral cancer, OSCC, small RNA-seq, microRNA, Coexpression network, WGCNA

Received: 09 Apr 2019; Accepted: 10 Sep 2019.

Copyright: © 2019 Dhahbi, Nunez-Lopez, Schneider, Victoria, Saccon, Bharat, McClatchey, Atamna, Scierski, Golusinski, Golusiński and Masternak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Joseph Dhahbi, California University of Science and Medicine, San Bernardino, United States,
Dr. Michal Masternak, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, 32827, Florida, United States,