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

## TL;DR

This study shows that the LINC02381/let-7g-5p/THBS1 pathway helps osteosarcoma grow and could be a new target for treatment.

## Contribution

The study identifies a novel ceRNA mechanism involving LINC02381, let-7g-5p, and THBS1 in promoting osteosarcoma progression.

## Key findings

- LINC02381 and THBS1 are upregulated, while let-7g-5p is downregulated in osteosarcoma tissues and cells.
- LINC02381 acts as a ceRNA to bind let-7g-5p, preventing it from suppressing THBS1.
- Inhibiting LINC02381 or overexpressing let-7g-5p reduces tumor growth and cell proliferation in osteosarcoma.

## Abstract

This study investigates the role of the LINC02381/let-7g-5p/THBS1 signaling axis in the progression of osteosarcoma (OS). The expression levels of LINC02381, let-7g-5p, and THBS1 were assessed in OS tissues and adjacent normal tissues using RT-qPCR, and their correlations with clinicopathological features were analyzed. Differential expression was further validated in OS cell lines and normal osteoblasts. Functional assays—including cell proliferation, colony formation, migration, and xenograft tumor growth—were conducted. The results indicated that LINC02381 and THBS1 were significantly upregulated, while let-7g-5p was downregulated in OS tissues and cells. Silencing LINC02381 or overexpressing let-7g-5p suppressed cell proliferation, reduced colony formation and migration, decreased THBS1 expression, and inhibited tumor growth in vivo. Mechanistically, LINC02381 acts as a competing endogenous RNA (ceRNA) by binding to let-7g-5p, thereby preventing let-7g-5p from downregulating THBS1. These findings imply that LINC02381 promotes OS progression via the let-7g-5p/THBS1 axis and may serve as a promising therapeutic target.

Objective: This study aimed to elucidate the regulatory mechanisms of the long intergenic non-protein coding RNA 02381 (LINC02381)/microRNA-let-7g-5p (let-7g-5p)/thrombospondin 1 (THBS1) signaling axis in osteosarcoma (OS). Methods: The expression levels of LINC02381, let-7g-5p, and THBS1 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 LINC02381 and let-7g-5p and the targeting relationship of let-7g-5p with THBS1 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. Results: Compared to adjacent normal tissues, LINC02381 and THBS1 were upregulated in OS tissues (fold change > 3.0, p < 0.001), while let-7g-5p was downregulated (fold change ≈ 0.038, p < 0.001). Similar expression trends were observed in U-2OS cells. Knockdown of LINC02381 or overexpression of let-7g-5p reduced cell proliferation, colony formation, migration, THBS1 expression, and tumor volume (p < 0.001). These inhibitory effects were partially reversed by let-7g-5p inhibitors, restoring cell viability and migration by approximately 70%. Mechanistically, LINC02381 functioned as a competing endogenous RNA (ceRNA), directly binding to let-7g-5p and mitigating its suppression of THBS1. Conclusions:
LINC02381 promotes OA progression by acting as a ceRNA for let-7g-5p, thereby upregulating THBS1 expression. This signaling axis represents a potential therapeutic target for OS.