Abstract
Early diagnosis of lung cancer greatly reduces mortality; however, the lack of suitable plasma biomarkers presents a major obstacle. Recent studies showed that long noncoding RNAs (lncRNAs) played important roles in cancer initiation and development. Here, we identified differentially expressed lncRNAs in 20 lung cancer samples by using custom designed microarray and evaluated their expression in 118 lung cancer samples by real-time PCR (qRT-PCR). lncRNA16 (ENST00000539303) expression was significantly higher in lung cancer tissues (80/118) than in adjacent matched normal tissues. Importantly, this increase was similar to that in plasma (53/84) of lung cancer patients, including early stage. The role of lncRNA16 in lung cancer was studied in vitro and in vivo by using the lung cancer cell lines and xenograft mouse models. The results reveal that knockdown of lncRNA16 inhibited proliferation of PC9 cells in vitro and also inhibited tumor growth in xenograft mouse models. Overexpression of lncRNA16 promoted proliferation of A549 cells in vitro and also promoted tumor growth in xenograft mouse models. Specifically, we showed that lncRNA16 promoted G2/M transition by regulating cyclin B1 transcription. Together, our findings suggest that lncRNA16 is a promising biomarker suitable for early diagnosis of lung cancer, and a potential target for lung cancer treatment.
Highlights
Lung cancer has been the leading cause of cancerrelated mortality worldwide [1, 2]
The results revealed that differential expression of ENST00000539303 was detected only in lung cancer, but not in other cancers
LncRNA16 expression was significantly higher in the lung cancer tissues than in adjacent matched normal tissues (Figure 1D–1F), indicating that lncRNA16 was already upregulated in the earliest stages of lung cancer
Summary
The overall 5-year survival rate after curative tumor resection is relatively low in patients with lung cancer [3], mainly because it is usually detected at an advanced stage. Methods for lung cancer diagnosis include the use of imaging and blood-fluid tests for tumor markers, both of which have limitations for early diagnosis. Tests for blood-fluid tumor markers are widely employed in cancer diagnosis, and several cancer biomarkers, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and neuronspecific enolase (NSE) [8,9,10], are used to diagnose lung cancer. Rate of false-negative results while detecting these biomarkers is commonly higher than 50%. These markers lack sufficient sensitivity for reliable diagnosis of lung cancer at an early stage [11, 12]. Identification of new and more sensitive biomarkers for diagnosisis of early stage lung cancer is of great urgency
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