Abstract. Lung cancer remains the leading cause of cancer-associated mortality in China and worldwide. Increasing numbers of studies have demonstrated that microRNAs (miRNAs/miRs) have vital functions in numerous developmental processes and tumorigenesis. The aim of the present study was to investigate miR-154 expression in non-small cell lung cancer (NSCLC), and to explore the roles of miR-154 in the carcinogenesis and progression of this cancer. Reverse transcription-polymerase chain reaction (RT-qPCR) was performed to detect miR-154 expression in NSCLC tissues and cell lines. In addition, cell proliferation assay, migration and invasion assays were adopted to investigate the functional roles of miR-154 in NSCLC. Bioinformatics analysis, luciferase reporter assay, RT-qPCR and western blot analysis were used to explore the potential targets of miR-154 in NSCLC. According to the results, miR-154 was significantly downregulated in NSCLC tissues and cell lines. Restoration of miR-154 expression inhibited proliferation, migration and invasion of NSCLC cells. In addition, B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) was identified as a direct target gene of miR-154 in NSCLC. In conclusion, miR-154 may function as a tumor suppressor in NSCLC, partly by regulating BMI-1, and the modulation of miR-154 expression represents a potential strategy for the treatment of NSCLC patients.
IntroductionLung cancer, a highly malignant tumor, is the leading cause of cancer-associated mortality in males and females worldwide (1). The incidence and mortality rates of non-small cell lung cancer are increasing in developing countries, including China, due to the increase in the use of tobacco as well as air pollution (2). According to its pathological pattern, lung cancer may be divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) (3). NSCLC, which includes adenocarcinoma, squamous cell carcinoma, adenosquamous cell carcinoma and large cell carcinoma, accounts for ~80-85% of all lung cancer cases (4). Despite advances in traditional treatments, including surgery, supplemented with radiotherapy and chemotherapy, the prognosis remains poor and the five-year overall survival rate is extremely low (17.1%) (5). These facts indicate an urgent requirement to fully understand the molecular mechanisms underlying the carcinogenesis and progression of NSCLC, and to investigate novel therapeutic targets to control this malignant disease.Increasing studies have demonstrated that microRNAs (miRNAs/miRs) have vital functions in numerous developmental processes and tumorigenesis, including the progression of NSCLC (6-8). miRNAs represent a group of small (~19-25 nucleotides), non-protein-coding, and endogenous single RNAs, which negatively regulate gene expression by binding to the 3' untranslated regions (3'UTRs) of target genes in an imperfect base pairing manner, causing mRNA cleavage or translational repression (9,10). To date, miRNAs have been demonstrated to regulate >30% of all cellular pro...