| Lung cancer is one of the most common cancers in the world with high mortality.Due to the limited development of cancer diagnostic technology,the diagnosis period of lung cancer is in the middle and late stage.The 5 year survival rate is less than 15%.With the aggravation of air pollution in recent years,lung diseases have seriously affected the health and living standards of human beings.Lung cancer can be divided into two types:small cell lung(SCLC)cancer and non-small cell lung cancer(NSCLC),of which NSCLC accounts for more than 80%of the whole lung cancer,and NSCLC mainly includes two types,squamous cell carcinoma and adenocarcinoma.As a common malignant tumor,although more and more clinical scientific research are reported about the diagnosis,treatment,prognosis and so on,the early diagnosis accuracy and accurate treatment still needs further exploration and verification,so it is important to discover the new model and mechanism about the NSCLC.MiR-494 has an important role in several types of human cancer,including non-small cell lung cancer(NSCLC).Although the role of miR-494 has been implicated in several studies,the expression profile and underlying mechanism is still poorly understood.In this study,by using qRT-PCR and Fisher’s exact test analysis,we found miR-494 is up-regated in NSCLC serum,and was related to clinical stage(P=0.005)and lymph node metastasis(P=0.001)with the highest difference compared with other microRNAs(miR-125a,miR-125b,miR-101-3p)between NSCLC and normal samples.MiR-125b was found with no difference between NSCLC and normal.In the clinicopathological staging of patients with NSCLC,the I-II phase was divided into early stage,and the III-IV phase was divided into late stage to study its significance in the early diagnosis of cancer.We found that miR-494 was significantly up-regated in III-IV compared to Ⅰ-Ⅱ of clinical stage and normal,which might work as potential tumor marker for early detection of NSCLC with high specificity and sensitivity.Moreover,Overexpression of miR-494 was confirmed to increase NSCLC proliferation,colony formation and cisplatin resistance by CCK-8 assays,colony formation assays,cisplatin toxicity assay and flow cytometry.We further showed that caspase-2(CASP2)is a functional target of miR-494 and expression of caspase-2 is inversely associated with miR-494 in vitro.MiR-494 was proved to promote proliferation and colony formation by directly targeting CASP2 in NSCLC cell lines.In addition,miR-494 reduces the sensitivity of NSCLC cells to cisplatin-induced toxicity and apoptosis through targeting CASP2.Therefore,our rests suggest that miR-494 plays an oncomiR role in NSCLC cells,and may be a candidate biomarker for malignant transformation and a therapeutic target of NSCLC.In conclusion,we focused on the function of miR-494 and CASP2 in NSCLC cells and first found that miR-494 cod regate proliferation,colony formation and cisplatin sensitivity through targeting CASP2,which may play a significant role in the development of lung cancer.In this paper,our study provides new insights into the function and molecar mechanism of miR-494 in NSCLC in vitro.This may open the door for using miRNA expression of some cancer cells as resistance marker or targets to improve response of resistant cells to cisplatin.Gene chip as a high-throughput method in recent years has assisted the biomedical researchers to study lncRNA expression profiles associated with NSCLC susceptibility.We analyzed mRNA and lncRNA expression profiles in the A549 cells with miR-494 overexpression using lncRNA microarray and the KEGG Pathway database.A large number of genes in TNF signaling pathway,NF-κB signaling pathway,apoptosis signaling pathway were significantly changed.These rests suggest new direction for the research of miR-494.In China,gastric cancer accounts for a large proportion of the leading causes of death,700 thousands people are diagnosed with gastric cancer each year accouting almost half of the world’s gastric cancer,and a small proportion of them is hereditary gastric cancer(HDGC).Hereditary gastric cancer,which have been defined by the IGCLC as follows:(1)two or more diffuse gastric cancer cases in first or second degree relatives,with at least one diagnosed before the age of 50,or(2)three or more diffiise gastric cancer cases in first or second degree relatives independent of age of onset,or(3)an individual diagnosed with diffuse gastric cancer before the age of 40,or(4)individuals and families diagnosed with both diflEuse gastric cancer and lobar breast cancer,with one diagnosed before the age of 50.With the rapid development of biotechnology,high-throughput gene expression detection has been applied rapidly.The detection based on cDNA Microarray and next-generation sequencing provides a concise and effective way for biomolecar research.In order to explore the influence of heredity on RNA level in gastric cancer,we used transcriptome analysis in diffuse gastric cancer tissues.We studied the changes of miRNA in the the biological characteristics of the target genes using the miRNA-seq_GO analysis of the miRNA target gene in biological process,cell composition and molecar function showed that there was no difference between them.Analysis of target gene KEGG signaling pathway indicates that miRNA target genes are more involved in neuromodation signaling pathway.Non genetic intestinal type gastric cancer is involved in protein digestion,absorption,adhesion and other signaling pathways.We used IncRNA chip to analyze the difference of mRNA and IncRNA.GO’s biological process analysis both focused on cell division related biological processes,and there was no significant difference between cell components and molecar function directions.KEGG signaling pathway analysis showed that hereditary gastric cancer was mostly involved in cell cycle and MAPK signaling pathway.Through the RNA analysis of hereditary and non-hereditary gastric cancer,we found that the function and molecar biology involved in signaling pathways provide an important research direction for the study. |
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