BJBMS MOLECULAR BIOLOGY Bosn J Basic Med Sci. 2020;20(3):347-356 347 www.bjbms.org living in developing countries. Therefore, the identification of the mechanisms of lung cancer development is a matter of urgency. MicroRNAs (miRNAs) are small non-coding RNA molecules, containing about 22 nucleotides [5]. These RNAs function in RNA silencing and post-transcriptional regulation of gene expression. Based on the evidence, microRNAs are involved in many cellular processes, such as cell proliferation [6], apoptosis [7], migration [8], invasion [9], epithelial-mesenchymal transition [10], and differentiation [11]. Moreover, the dysregulation of microRNAs also contributes to the development and metastasis of many cancers, such as lung [12], breast [13], gastric [14], ovarian [15], and liver cancers [16].Recent data are indicative of the significantly lower expression of microRNA-608 in lung cancer tissues than in the adjacent normal tissues [17]. Furthermore, another report also revealed that the upregulation of microRNA-608 could increase cell death in A549 and SK-LU1 cells [18]. The results of the aforementioned studies are indicative of the involvement of microRNA-608 in the progression of lung cancer. However, the relationship between microRNA-608 and lung cancer and the molecular mechanism remain to be revealed.
ABSTRACTLung cancer is the leading cause of cancer-related mortality around the world. This malignancy has a 5-year survival rate of 21%, because most of the patients are diagnosed in the middle or late stage of the disease when local metastasis and tumor invasion have already progressed. Therefore, the investigation of the pathogenesis of lung cancer is an issue of crucial importance. MicroRNAs (miRNAs) seem to be involved in the evolution and development of lung cancer. MicroRNA-608 is likely to be downregulated in lung cancer tissues. Regarding this, the current study involved the determination of the fundamental mechanism of microRNA-608 in the development of lung cancer. Based on the results of quantitative reverse transcription polymerase chain reaction (RT-qPCR), the expression level of microRNA-608 was downregulated in 40 lung cancer tissues, compared to that in the adjacent normal tissues. The results of dual-luciferase reporter assay revealed that bromodomain-containing protein 4 (BRD4) was the direct target of microRNA-608. Accordingly, the lung cancer tissues had an elevated expression level of BRD4, in contrast to the adjacent normal tissues. The results of Cell Counting Kit 8 assay demonstrated that the high expression of microRNA-608 notably restrained lung cancer cell proliferation. The scratch wound and transwell assays showed that the upregulation of microRNA-608 suppressed the migration and invasion of lung cancer cells. Finally, the western blot assay showed that in the microRNA-608 mimics group, the expression levels of BRD4, p-JAK2, p-STATA3, CD44, and MMP9 were significantly decreased, compared with those in the negative control miRNA mimics group. Our results indicate that high expres...