The LINC02381/let-7g-5p/THBS1 Signaling Axis Modulates Cellular Proliferative Activity in Osteosarcoma

<b>Objective:</b> This study aimed to elucidate the regulatory mechanisms of the long intergenic non-protein coding <i>RNA 02381</i> (<i>LINC02381</i>)/<i>microRNA-let-7g-5p</i> (<i>let-7g-5p</i>)/<i>thrombospondin 1</i> (<i>THBS1</i>) signaling axis in osteosarcoma (OS). <b>Methods:</b> The expression levels of <i>LINC02381</i>, <i>let-7g-5p</i>, and <i>THBS1</i> were quantified in OS and adjacent normal tissues via reverse transcription quantitative polymerase chain reaction. Their correlations with clinicopathological features were analyzed. Expression patterns were further validated in OS cell lines (143B, U-2OS, Saos-2, MNNG-HOS, MG-63) and normal osteoblast cell line hFOB1.19. The molecular interaction between <i>LINC02381</i> and <i>let-7g-5p</i> and the targeting relationship of <i>let-7g-5p</i> with <i>THBS1</i> were verified via dual-luciferase reporter and RNA pull-down assays. Functional effects were assessed using cell counting kit-8, colony formation, Transwell migration, and xenograft tumor models. <b>Results:</b> Compared to adjacent normal tissues, <i>LINC02381</i> and <i>THBS1</i> were upregulated in OS tissues (fold change > 3.0, <i>p</i> < 0.001), while <i>let-7g-5p</i> was downregulated (fold change ≈ 0.038, <i>p</i> < 0.001). Similar expression trends were observed in U-2OS cells. Knockdown of <i>LINC02381</i> or overexpression of <i>let-7g-5p</i> reduced cell proliferation, colony formation, migration, <i>THBS1</i> expression, and tumor volume (<i>p</i> < 0.001). These inhibitory effects were partially reversed by <i>let-7g-5p</i> inhibitors, restoring cell viability and migration by approximately 70%. Mechanistically, <i>LINC02381</i> functioned as a competing endogenous RNA (ceRNA), directly binding to <i>let-7g-5p</i> and mitigating its suppression of <i>THBS1</i>. <b>Conclusions:</b><i>LINC02381</i> promotes OA progression by acting as a ceRNA for <i>let-7g-5p</i>, thereby upregulating <i>THBS1</i> expression. This signaling axis represents a potential therapeutic target for OS.