FGF-induced LHX9 regulates the progression and metastasis of osteosarcoma via FRS2/TGF-β/β-catenin pathway

Abstract

Background: Fibroblast growth factor (FGF) and tumor growth factor-β (TGFβ) have emerged as pivotal regulators during the progression of osteosarcoma (OS). LHX9 is one crucial transcription factor controlled by FGF, however, its function in OS has not been investigated yet. Methods: The expression of LHX9, FRS2, BMP4, TGF-beta R1, SMAD2, beta-catenin and metastasis-related proteins was measured by real-time quantitative PCR (RT-qPCR) and Western blot. CCK-8 assay and colony formation assay were employed to determine the proliferation of OS cells, while scratch wound healing assay and transwell assay were used to evaluate their migration and invasion, respectively. In vivo tumor growth and metastasis were determined by subcutaneous or intravenous injection of OS cells into nude mice. Results: LHX9 expression was evidently up-regulated in OS tumor tissues and cell lines. Knockdown of LHX9 impaired the proliferation, migration, invasion and metastasis of OS cells. Mechanistically, LHX9 silencing led to the downregulation of BMP-4, β-catenin and metastasis-related proteins, which was also observed in beta-catenin knockdown OS cells. By contrast, FRS2 knockdown conduced to the up-regulation of LHX9, BMP4, β-catenin and TGF-βR1, while TGF-beta inhibition repressed the expression of LHX9 and metastasis-related proteins. Additionally, let-7c modulates LHX9 and metastasis-related proteins by suppressing TGF-beta R1 expression on transcriptional level. Conclusions: This study revealed LHX9 was essential for the proliferation, migration, invasion, and metastasis of OS cells via FGF and TGF-β/β-catenin signaling pathways.

CHRDL2 promotes osteosarcoma cell proliferation and metastasis through the BMP‐9/PI3K/AKT pathway

“…Increasing the expression of BMP‐7 indicated the enhanced proliferation and migration of osteosarcoma cells (Jiang et al, 2017). However, BMP‐4 which regulated by LIM homeobox 9 inhibited the development of osteosarcoma (Li et al, 2019). BMP‐2 had potential to inhibit the stemness of osteosarcoma cells (Wang et al, 2011).…”

Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

“…Osteosarcoma is a common primary bone malignancy that mainly affected children and adolescents (1). In spite of substantial achievement in diagnosis and treatment, the 5-year survival of osteosarcoma remains unsatisfied (2), largely due to the insufficiency of accurate predictive biomarkers (3).…”

miR-497 inhibits tumor growth and migration of osteosarcoma by targeting plexinA4 and CDK6

“…e treatments for osteosarcoma include surgery, radiotherapy, chemotherapy, or a combination of modalities. Despite improvements in diagnostic and therapeutic techniques, the 5-year survival rates for patients with osteosarcoma have not increased over the last 20 years [3,4]. e potentially high incidence of morbidity and low cure rate urgently require novel methods for diagnosing and treatments which rely on biomedical research.…”