LRRC3-DT Inhibits Malignant Behaviors of Hepatocellular Carcinoma and is Associated With CCDC81 Expression

Background: Enhancer RNAs (eRNAs) are important regulators of tumor development and progression. Nevertheless, the diagnostic utility of circulating eRNAs in hepatocellular carcinoma (HCC) remains unclear. Methods: This was a retrospective study. The recently identified eRNA, leucine-rich repeat-containing 3 divergent transcript (LRRC3-DT), was analyzed in serum samples, tissue specimens, and various cell lines. Its diagnostic performance was evaluated alone and in combination with alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) using receiver operating characteristic (ROC) curve analysis. Functional investigations were performed to assess the biological role of LRRC3-DT by overexpressing and knocking down this eRNA in HCC cell lines. Furthermore, using transcriptome sequencing, potential target genes of LRRC3-DT were identified. Results: The serum levels of LRRC3-DT were significantly lower in patients diagnosed with HCC than in healthy controls. When LRRC3-DT was assessed alongside AFP and PIVKA-II, the combination improved sensitivity for the detection of HCC. Despite earlier research indicating that LRRC3-DT is present primarily in the nucleus and is strongly associated with tumor proliferation, invasion, and apoptosis, the serum levels of LRRC3-DT were similar between patients with HCC and those with benign liver diseases in the present study. These findings indicate limited specificity in distinguishing between these two conditions. Conclusions: Serum LRRC3-DT represents a potential auxiliary biomarker for early HCC screening; its combined use with other indicators improved diagnostic performance. However, it cannot individually discriminate HCC from benign liver disorders, and additional validation studies are warranted to confirm its differential diagnostic value.