The Mechanism Of MiR-182-cytokine Regulation Axis In Bone Metastasis Of Lung Cancer

Lung cancer is the leading cause of cancer-related deaths in the world,which has the highest incidence and mortality in China.Bone metastasis of lung cancer is an important cause of high mortality of lung cancer,with a incidence of 30-40% and a 5-year survival rate of less than 5%.Once bone metastasis of lung cancer occurs,it will cause bone pain,pathological fracture,hypercalcemia,spinal cord compression syndrome and other bone related events(SREs),which will seriously affect the quality of life of patients.Studies have shown that miRNA plays an important role in tumor development and metastasis,and the level of miRNA in serum is closely related to tumor progression.Therefore,by exploring the role of miRNA in bone metastasis of lung cancer and its mechanism,this study provides new molecular markers and therapeutic targets for early diagnosis and treatment of bone metastasis of lung cancer.In this study,it was found that the expression level of miR-182 in lung cancer tissues of lung cancer patients was significantly higher than that in paracancer tissues,and the expression level of miR-182 in bone metastasis tissues of lung cancer patients was significantly higher than that of lung cancer patients without metastasis.Subsequently,MTT and osteoclast differentiation experiments showed that miR-182 could promote the proliferation of lung cancer cells and osteoclast differentiation.Then,KLHL21 was predicted and identified as the target gene of miR-182 through target prediction software and Dual-luciferase reporter gene assay.Furthermore,a series of experiments demonstrated that miR-182 could promote the secretion of IL-8 and IL-1α by activating NF-κB signaling pathway through targeted down-regulation of KLHL21,thereby promoting the proliferation of lung cancer cells and osteoclast differentiation,thus playing a role in promoting bone metastasis of lung cancer.In summary,this study explores and confirms the role of the miR-182/KLHL21/NF-κB/(IL-8,IL-1α)axis in lung cancer bone metastasis,providing new molecular markers and therapeutic targets for the early diagnosis and treatment of lung cancer bone metastasis.