Abstract
MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.
Highlights
Lung cancer is the leading cause of cancer death worldwide, with increasing incidence and mortality
Compared with matched adjacent noncancerous tissues, miR-944 levels were significantly decreased in the 11 cases of non-small cell lung cancer (NSCLC) tissues (Figure 2C). These results indicated that the reduced expression of miR-944 was a frequent event in NSCLC cell lines and tissues, implying that miR-944 may be involved in lung carcinogenesis
To verify the sequencing data, we examined the expression of miR-944 in NSCLC cell lines and clinical NSCLC specimens using Quantitative Real-Time PCR (qRT-PCR) and found that miR-944 was downregulated in the majority of NSCLC cell lines and tissues used in this study
Summary
Lung cancer is the leading cause of cancer death worldwide, with increasing incidence and mortality. Among all types of lung cancer, non-small cell lung cancer (NSCLC) is the most common type, occurring in approximately 85% of cases [1]. Some progress has been made in clinical and experimental oncology, the prognosis of NSCLC is still dismal and the 5-year survival rate is approximately 15% [2]. Understanding the molecular mechanism of cancer development and progression is crucial for early diagnosis and effective treatment. Further exploration of the underlying mechanism of NSCLC is still urgently needed to generate more effective diagnosis and treatment of NSCLC. Accumulating reports have described that microRNAs (miRNAs) are implicated in the initiation and progression of lung cancer [4]
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