Abstract
Increasing evidence has indicated that long non‑coding RNAs (lncRNAs) serve an essential role in carcinogenesis and cancer development. It has been reported that lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT‑AS1) serves a crucial role in several types of cancer. However, the clinical significance of circulating NNT‑AS1 expression in colorectal cancer (CRC) remains to be elucidated. The current study aimed to investigate the potential role of NNT‑AS1 and the clinical significance of its serum expression levels in patients with CRC. The expression of NNT‑AS1 was measured in 40 pairs of tumor and adjacent normal tissues from patients with CRC via reverse transcription‑quantitative PCR. The serum expression levels of NNT‑AS1 were assayed in an independent cohort of healthy controls and patients with CRC. The levels of NNT‑AS1 were also compared between paired preoperative and postoperative serum samples. In addition, the presence of exosomal NNT‑AS1 in serum was explored. Furthermore, the biological roles of NNT‑AS1 were investigated in CRC cells in vitro. The expression of NNT‑AS1 was significantly upregulated in tumor tissues compared with adjacent normal tissues (P<0.05). A higher level of NNT‑AS1 was associated with an advanced CRC stage. The serum levels of NNT‑AS1 were significantly upregulated in patients with CRC compared with healthy subjects (P<0.05). Furthermore, the NNT‑AS1 levels were significantly decreased in postoperative samples compared with preoperative samples (P<0.01). In addition, it was also identified that NNT‑AS1 was upregulated in CRC exosomes (P<0.01), whereas no significant difference was observed in NNT‑AS1 levels between serum and exosomes. Silencing of NNT‑AS1 inhibited the proliferation, migration and invasion of CRC cells. It was also identified that NNT‑AS1 exerted its effects via regulation of the microRNA‑496/Ras‑related protein Rap‑2c axis. The present study demonstrated that circulating NNT‑AS1, which may be protected by exosomes, could be a novel potential biomarker and therapeutic target in CRC.