Long Non-Coding RNA CTD-2245E15.3 Drives Proliferation and Migration in Gastrointestinal Stromal Tumors

<b>Background:</b> Long non-coding RNAs (lncRNAs) participate in a wide range of physiological processes, and their dysregulation is prevalent in human cancers, indicating critical roles in tumorigenesis. In intermediate- to high-risk gastrointestinal stromal tumors (GISTs), resistance to tyrosine kinase inhibitors (TKIs) remains a major therapeutic challenge. Therefore, identifying lncRNAs as potential novel therapeutic targets is of considerable interest. <b>Methods:</b> Three paired samples of intermediate- to high-risk GIST tissues and adjacent normal tissues were subjected to transcriptome sequencing. High-content screening (HCS) was subsequently performed to identify candidate lncRNAs with significant effects on GIST cell proliferation. Loss-of-function experiments were conducted, and cell proliferation, migration, and apoptosis were evaluated using the Cell Counting Kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, and flow cytometry, respectively. In addition, in situ hybridization (ISH) was performed on 507 primary GIST tissue specimens to examine the association between CTD-2245E15.3 expression and clinicopathological features, including progression-free survival (PFS) and overall survival (OS). <b>Results:</b> Transcriptome sequencing revealed 2924 upregulated and 2629 downregulated lncRNAs in GIST tissues compared with adjacent normal tissues. Based on HCS results, CTD-2245E15.3 was selected for further functional analyses. CCK-8 assays demonstrated that knockdown of CTD-2245E15.3 significantly inhibited proliferation of GIST cells. Consistently, colony formation and migratory capacity were markedly reduced in the shCTD-2245E15.3 group compared with controls. Furthermore, flow cytometric analysis showed a significant increase in apoptosis following CTD-2245E15.3 silencing. ISH analysis revealed that high CTD-2245E15.3 expression correlated with adverse clinicopathological features and poorer PFS and OS. <b>Conclusions:</b> Our study demonstrates that CTD-2245E15.3 promotes proliferation and migration of GIST cells and is associated with poor prognosis, highlighting its potential as a therapeutic target and diagnostic biomarker.