Hsa-let-7g promotes osteosarcoma by reducing HOXB1 to activate NF-kB pathway

• Published in: Biomedicine & pharmacotherapy Vol. 109; pp. 2335 - 2341
• Main Authors: Zhou, Jian-Lin, Deng, Shuang, Fang, Hong-Song, Yu, Guangyang, Peng, Hao
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2019; Elsevier
• Subjects: HOXB1; Metastasis; microRNAs; NF-kB; Osteosarcoma; microRNAs; Metastasis; HOXB1; Osteosarcoma; NF-kB
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.11.026

A schematic model of Hsa-let-7 g–HOXB1–NF-kB signaling pathway in osteosarcoma. Mature hsa-let-7 g can bound HOXB1, resulting in downregulation of HOXB1 expression. Meanwhile, NF-kB passway is activated by the overexpression of hsa-let-7 g and downregulation of HOXB1. [Display omitted] •Osteosarcoma tissues have higher Hsa-let-7 g but lower HOXB1 when compared with normal tissues.•Osteosarcoma patients with high expression of hsa-let-7 g have poorer prognosis.•hsa-let-7 g promotes cell proliferation and tumor formation in vitro and in vivo.•hsa-let-7 g modulates NF-κB activation, as well as inhibition of HOXB1 in vitro and in vivo. MicroRNA (miRNA) is known to be involved in regulating the proliferation, migration and apoptosis of cancer cells in osteosarcoma. In this study, We aim to explore the expression of hsa-let-7 g and its role in pathogenesis of osteosarcoma. By analyzing clinical data. We found high expression of hsa-let-7 g in patients with osteosarcoma. The patients with higher expression of hsa-let-7 g showed poorer prognosis and lower survival rate. After downregulation of hsa-let-7 g in cell model and animal model, we found that with downregulation of hsa-let-7 g, the proliferation of osteosarcoma cells was significantly reduced, the level of migration and invasion was down-regulated, the cell cycle was inhibited, and cell apoptosis was increased. Through Dual Luciferase Reporter, immunohistochemistry, western blot and other experiments, it was found that hsa-let-7 g down-regulated HOXB1 gene and activated NF-kB pathway to promote the development of osteosarcoma. In conclusion, hsa-let-7 g is highly expressed in osteosarcoma tissues, and high expression of hsa-let-7 g can promote the occurrence of osteosarcoma by down-regulating HOXB1 and activating NF-kB pathway.