The Function And Application Of MicroRNA In Non-small Cell Lung Cancer

Lung cancer is the most common malignance and the leading cause of cancer-related death worldwide,of which the non-small cell lung cancer(NSCLC)accounts for about 85% of all lung cancer cases.The high mortality rate and poor prognosis of NSCLC was mainly induced by two aspects: first,in currently there is no effective methods for early detection of lung cancer,resulting in that the most patients with lung cancer were first diagnosed at late stage;second,lung cancer is prone to distant metastasis,especially bone metastasis,which accounting for about30% of all the metastatic cases.Nowadays,there are more and more evidence supports that microRNAs(miRNAs)play a important role in the proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and distant metastasis of tumor cells.Meanwhile,the miRNAs level in serum is closely related to the tumorigenensis and developments.So,we studied from two aspects to explore the mechanism and application of miRNAs in NSCLC.In one hand,we screened serum miRNAs to be biomarkers for early detection of adenocarcinoma,and the other hand,we studied the molecular mechanism of miRNA in NSCLC bone metastasis.In the first aspect,we collected serum samples from 180 patients with adenocarcinoma and 180 healthy controls.Serum miRNAs profiling was performed by low-density array(LDA)using RNA extracted from blood samples of 20 patients and 20 controls.To validate the selected miRNAs,a stem-loop based RT-q PCR assay was used and serum samples from 160 patients and 160 controls were examined.As the result,a panel of miRNA with miR-146 a,miR-222 and miR-223 could be used as potential noninvasive biomarkers for early detection of AD.In the other aspect,through the validation of our previous study,we found that miR-182 expression level in the NSCLC cell line A549 BM,which is prone to metastasis to bone,is significantly higher than the NSCLC cell lines that have no metastasis ability or not to metastasis to bone.Then,we found miR-182 exerts a tumor-promoting effect in A549 BM by MTT and Transwell assay.After that,we validated that MUNB is the target of miR-182 after the prediction through predict tools.And then,we found that NUMB can interrupt the Notch signaling pathway through block the intracellular domain of the Notch receptor(NICD).In brief,miR-182 exerts the tumor-promoting effect by suppressing the expression of NUMB,reducing the Notch interruption by NUMB.In summary,we screened a panel of miRNA including miR-146 a,miR-222 and miR-223 could be used as potential noninvasive biomarkers for early detection of adenocarcinoma.Meanwhile,we explored the molecular mechanism of miR-182 in NSCLC bone metastasis,providing new clues for clinically prevention and therapeutic strategy.