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

Abstract

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 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 (<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 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.

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2026-03-05
2026-03-08

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/content/journals/cmc/10.2174/0109298673454702260121191612
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Reduced Expression of LINC01515 Suppresses Proliferation and Invasion of Lung Adenocarcinoma Cells via Modulation of the miR-33a-5p/HMGA2 Signaling Axis
Bentham Science Publishers ; https://doi.org/10.2174/0109298673454702260121191612
/content/journals/cmc/10.2174/0109298673454702260121191612
/content/journals/cmc/10.2174/0109298673454702260121191612
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  • Article Type:     Research Article
Keywords: miR-33a-5p ; LINC01515 ; lung adenocarcinoma ; migration ; RNA ; proliferation

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