tRF‐3a‐Pro: A Transfer RNA‐Derived Small RNA as a Novel Biomarker for Diagnosis of Hepatitis B Virus‐Related Hepatocellular Carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is one of the most challenging malignancies of the digestive system. Screening for novel biomarkers and therapeutic targets is a promising strategy to enhance HCC prognosis. Recently, liquid biopsy with circulating nucleic acids as the detection targets has attracted much attention in the field of early screening of tumours. However, the diagnostic value and biological functions of transfer RNA‐derived small RNAs (tsRNAs) in serum, particularly in HCC, remains unknown. In this study, we characterised the expression profile of tsRNAs in hepatitis B virus (HBV)‐related HCC, and confirmed the diagnostic potential of serum tRF‐3a‐Pro. On this basis, we established a diagnostic model that integrates tRF‐3a‐Pro with the classic HCC biomarker alpha‐fetoprotein (AFP) through logistic regression analysis. Besides, both in vivo and in vitro experiments demonstrated that tRF‐3a‐Pro, a highly expressed tsRNA, promotes HCC cell proliferation. These findings suggested that tRF‐3a‐Pro could serve as a novel biomarker for HBV‐related HCC.