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

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 non-coding 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.