Reduced Expression of LINC01515 Suppresses Proliferation and Invasion of Lung Adenocarcinoma Cells via Modulation of the miR-33a-5p/HMGA2 Signaling Axis

Objective: This study examined the regulatory mechanisms and functional significance of LINC01515 in lung adenocarcinoma (LUAD) cells. Methods: Associations between LINC01515 levels and patient survival were analyzed using TCGA data, and qRT-PCR was employed to assess LINC01515 transcript levels in both LUAD tissues (n = 15) and cell lines. Following LINC01515 silencing, changes in migration, proliferation, cellular viability, and invasion were evaluated using colony formation, CCK-8, and Transwell assays. Bioinformatics predictions of relationships among LINC01515, miR-33a-5p, and HMGA2 were confirmed using dual-luciferase reporter assays. Functional cellular experiments further verified that LINC01515 modulates both growth and motility via the miR-33a-5p/HMGA2 regulatory axis, and mouse xenograft models were employed to determine the effects of LINC01515 depletion on tumor development. Results: Compared with matched normal controls, LINC01515 levels were markedly higher in LUAD tissues (p<0.01). Moreover, both cellular and animal functional tests revealed that LINC01515 silencing significantly decreased cell motility, colony-forming capacity, proliferation, and invasive potential. Further mechanistic investigations showed that LINC01515 acts as a competing endogenous RNA by sequestering miR-33a-5p, thereby alleviating the suppression of HMGA2 expression. Moreover, rescue assays confirmed that the regulatory interplay among LINC01515, miR-33a-5p, and HMGA2 is a key determinant of LUAD cell proliferation and motility. Discussion: These data identify LINC01515 as an oncogenic driver of LUAD via a cytoplasmic ceRNA mechanism that derepresses HMGA2 through miR-33a-5p. Clinically, measuring LINC01515 may aid risk stratification and prognosis, and therapeutically, targeting LINC01515 or restoring the miR-33a-5p/HMGA2 balance represents a tractable axis to curb LUAD growth and dissemination, extending the lncRNA-based framework for precision oncology. Conclusion: LINC01515 is predominantly distributed in the cytoplasm of LUAD cells and promotes oncogenic behavior through modulation of the miR-33a-5p/HMGA2 axis, suggesting the potential of LINC01515 as a biomarker and target in LUAD management.