The role of AGAP2-AS1, DLEU2, HMBOX1_1, and UGDH-AS1 in the progression of esophageal squamous cell carcinoma

Long noncoding RNAs (lncRNAs) have been recognized as viable prognostic and therapeutic indicators for numerous human malignancies. Nonetheless, the operational roles and fundamental mechanisms of important lncRNAs that impact esophageal squamous cell carcinoma (ESCC) remain predominantly obscure. Recently, lncRNAs have been identified to exert regulatory influence on epithelial-mesenchymal transition (EMT) via intricate interplay with EMT-associated transcription factors (TFs) and signaling pathways. The current experimental study aimed to elucidate the expression of four lncRNAs in ESCC patients and explain their potential involvement in the EMT process and the pathogenesis of ESCC.

In the study, the expression levels of lncRNAs (AGAP2-AS1, DLEU2, HMBOX1_1 (AC108449.2), and UGDH-AS1) and mRNAs (TWIST1, MMP13, and CD44S) between fifty ESCC and adjacent normal tissue samples were measured using quantitative real-time PCR.

The upregulation of CD44S (36%), TWIST1 (52%), DLEU2 (58%), AGAP2-AS1 (62%), and MMP13 (74%), were indicated in ESCC samples, while the downregulation of UGDH-AS1 and HMBOX1_1 were found in 62% and 64% of patients, respectively. The expression levels of lncRNAs and EMT-related markers were found to be significantly correlated in several patient clinicopathological traits (P < 0.05), representing correlations between AGAP2-AS1, DLEU2, HMBOX1_1 (AC108449.2), and UGDH-AS1 with EMT status in ESCC.

Our results have unveiled that these lncRNAs, which regulate EMT, may play a crucial role in the regulatory process of EMT via the CD44S-TWIST1-MMP13 axis. Moreover, it may be assumed that lncRNAs present a promising avenue for both diagnosis and therapeutic intervention in the context of ESCC.