Abstract
Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was determined. Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. We demonstrated that miR-3607-3p was downregulated in NSCLC tissues and that miR-3607-3p might act as an independent predictor for overall survival in NSCLC. Moreover, serum miR-3607-3p may be a novel and stable marker for NSCLC. We found that overexpression of miR-3607-3p inhibited cell proliferation, colony formation, migration and invasion, and hampered the cell cycle of NSCLC cell lines in vitro. Our results suggested that miR-3607-3p directly targets TGFBR1 and CCNE2. In accordance with in vitro studies, we confirmed that miR-3607-3p functions as a potent suppressor miRNA of NSCLC. We showed that miR-3607-3p agomir could reduce tumor growth and inhibit TGFBR1 and CCNE2 protein expression. Taken together, our findings indicate that miR-3607-3p can inhibit NSCLC cell growth and metastasis by targeting TGFBR1 and CCNE2 protein expression, and provide new evidence of miR-3607-3p as a potential non-invasive biomarker and therapeutic target for NSCLC.
Highlights
Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in developed and developing countries [1]
We first showed downregulation of miR-3607-3p in non-small cell lung carcinoma (NSCLC) tissues and demonstrated that miR-3607-3p may act as an independent predictor of overall survival
To determine the potential functions of miR-3607-3p in NSCLC pathogenesis, we analyzed the expression of miR-3607-3p in 162 NSCLC tissue samples compared with their adjacent normal lung tissues. miR-3607-3p staining in NSCLC tissues was negative or weak relative to normal the adjacent normal lung tissues that exhibited light to dark staining (Fig 1)
Summary
Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in developed and developing countries [1]. It was estimated that there were 1,241,600 new cases of lung cancer in males and 583,100 in females in 2014 [1]. In China, it is estimated that approximately 733,300 new cases were diagnosed and 610,200 patients died of lung cancer in 2015 [2]. 85% of lung cancers are classified histopathologically as non-small cell lung carcinoma (NSCLC) [3]. Poor outcomes and frequent relapses associated with lung cancer urgently demand the development of new screening and early biomarkers for the accurate and non-invasive detection of lung cancer metastasis and recurrence [5]. Since pathologically diagnosing all suspicious nodules is currently impossible, a noninvasive and easy sampling strategy that provides reliable information on the metastatic state of NSCLC is urgently required
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