IL-8-Mediated MicroRNA In Lung Cancer Bone Metastasis

Lung Cancer is still the most fatal malignant tumor in the world,for its high tumor heterogeneity and low five-year survival rate,which seriously threatens human health.At present,the diagnosis of early lung cancer is still lack of effective indicators,patients often develop to the late stage to be confirmed,seriously delayed the time of treatment.In addition,distant metastasis is easy to occur,especially bone metastasis,which is also an important cause of high mortality of lung cancer.Based on the above situation,non-invasive biomarkers with high sensitivity and specificity is urgently needed in early diagnosis of lung cancer.Besides,we need to actively explore the molecular mechanism of bone metastasis in lung cancer,in order to improve the detection rate of early lung cancer,and reduce the mortality of lung cancer patients.On the one hand,we collected bronchial alveolar lavage fluid from 405 patients with suspected lung cancer deseases,and detected the abbrent methylation changes of the SHOX2 and RASSF1 A gene with a new RT-PCR kit.Our data suggested that when used as a panel,the two gene achieved high diagnostic sensitivity and specificity in lung cancer diagnosis.In addition,this methylation panel showed high diagnostic ability in early stage lung cancer patients,which demonstrates to be an effective biomarker of lung cancer.On the other hand,we found that the level of IL-8 in lung cancer patients with bone metastases is higher than that in patients without bone metastases.By miRNA sequencing and functional experiments,IL-8 showed the tumor-promoting ability by increasing the level of miR-182.Further,we validated that NUMB is the target of miR-182 through target prediction tools.After a series of in vitro experiments,we found that miR-182 exerts the tumor-promoting effect through Notch signaling pathway by reducing the inhibitory effect of NUMB on NICD.Generally speaking,our study found that the SHOX2 and RASSF1 A methylation panel can be used as a noninvasive biomarker for early detection of lung cancer.Meanwhile,we explored the molecular mechanism of IL-8-miR-182 axis in lung cancer bone metastasis,which provides new clues for clinically prevention and therapeutic strategy of lung cancer.