HOXB5 promotes the progression and metastasis of osteosarcoma cells by activating the JAK2/STAT3 signalling pathway

Qiming Ma; Xingxing Li; Huming Wang; Shenglin Xu; Yukang Que; Peng He; Rui Yang; Qiwei Wang; Yong Hu

doi:10.1016/j.heliyon.2024.e30445

HOXB5 promotes the progression and metastasis of osteosarcoma cells by activating the JAK2/STAT3 signalling pathway

Heliyon. 2024 Apr 29;10(9):e30445. doi: 10.1016/j.heliyon.2024.e30445. eCollection 2024 May 15.

Authors

Qiming Ma¹, Xingxing Li^{1

2}, Huming Wang¹, Shenglin Xu¹, Yukang Que¹, Peng He¹, Rui Yang¹, Qiwei Wang², Yong Hu¹

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
² Department of Orthopedics, Lu 'an Hospital of Anhui Medical University, Lu'an, 237008, Anhui, China.

Abstract

Objective: To investigate the involvement of the homeobox gene B5 (HOXB5) in the progression and metastasis of osteosarcoma.

Methods: The expression of HOXB5 in human osteosarcoma tissues and its correlation with clinical indicators were investigated using bioinformatics analysis and immunohistochemical labelling. Human osteosarcoma cells (HOS, MG63, U2OS, and Saos-2) and normal human osteoblasts (hFOB1.19) were cultivated. The expression of HOXB5 in these cells was detected using western blotting (WB) and RT‒PCR. Two cell lines exhibiting elevated HOXB5 expression were chosen and divided into three groups: the blank group (mock), control group (control) and transfection group (shHOXB5). The transfection group was infected with lentivirus expressing shRNAs targeting HOXB5. The transfection efficiency was detected by WB. Cell proliferation suppression was measured by CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays; the percentage of apoptotic cells was determined by flow cytometry; and cell migration and invasion were detected via the Transwell chamber test. WB was utilized to determine the protein expression of genes linked to metastasis (MMP2, MMP9), apoptosis (Bax, Bcl-2), and the JAK2/STAT3 pathway (JAK2, p-JAK2, STAT3, p-STAT3).

Results: In osteosarcoma tissues, HOXB5 expression was elevated and strongly correlated with distant metastasis. Silencing HOXB5 reduced the proliferation, migration and invasion of osteosarcoma cells; prevented the progression and metastasis of tumours in tumour-bearing nude mice; and reduced the activation of key proteins in the JAK2/STAT3 signalling pathway.

Conclusion: Through the JAK2/STAT3 signalling pathway, HOXB5 plays a crucial role in the malignant progression of osteosarcoma and is a promising target for osteosarcoma treatment.

Keywords: HOXB5; JAK2/STAT3 pathway; Metastasis; Osteosarcoma; Progression.