Abstract
The expression patterns of the long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) have not been investigated in the context of cancer. In this study, we aim to investigate the NNT-AS1 expression level in colorectal cancer (CRC) patients and its potential roles in tumor biology. We measured the expression of NNT-AS1 in 70 paired tumor tissues and adjacent normal tissues. NNT-AS1 was expressed higher in tumor tissues than that in adjacent noncancer tissues, and higher expression of NNT-AS1 was significantly correlated with lymph node metastasis (Yes vs. No, P=0.004), TNM stage (I/II vs. III/IV, P=0.004), vessel invasion (Yes vs. No, P=0.002) and differentiation (well and moderate vs. poor, P=0.008). Multivariate analyses revealed that NNT-AS1 expression was an independent predictor of overall survival (P=0.0174) and progression free survival (P=0.0132) for CRC. Knockdown of NNT-AS1 using small interfering RNA (siRNA) significantly impaired CRC cell proliferation, migration and invasion in vitro and silencing NNT-AS1 also suppressed tumor growth and metastasis in nude mice. The western blot experiments revealed that silencing NNT-AS1 inhibited epithelial-mesenchymal transition (EMT) and inactivated MAPK/Erk signaling pathway in CRC cell lines. In conclusion, our studies implied that NNT-AS1 may involve in the development and progression of CRC via its regulation of cell proliferation, migration, and invasion by NNT-AS1-mediated activating of MAPK/Erk signaling pathway and EMT. NNT-AS1 may be a useful diagnostic and prognostic biomarker and a potential therapeutic target in CRC patients.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer-related death in the world
We have shown that the expression level of Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) in colorectal cancer (CRC) cancer tissues was higher than that in adjacent noncancerous tissues
In CRC cell models, knocking down nicotinamide nucleotide transhydrogenase (NNT)-AS1 resulted in significantly reduced proliferation, migration, invasion in vitro and in vivo through downregulating the Mitogen activated protein kinase (MAPK)/Erk signaling pathway and inhibiting epithelialmesenchymal transition (EMT)
Summary
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer-related death in the world. LncRNAs can mediate genes activation and inactivation by chromatin remodeling, such as Hox transcript antisense intergenic RNA (HOTAIR), X inactive specific transcript (XIST). They can regulate the functions of cells, such as differentiation, apoptosis www.impactjournals.com/oncotarget and cell cycle by transferring the chromatin-modifying complexes to the promoters of important genes [4, 5]. They can participate in transcriptional and posttranscriptional processing and protein modulating by binding to proteins [6], inhibiting promoters [7], interacting with transcription factors [8], or acting as endogenous sponges to sequester microRNAs [9]. With the above molecular mechanisms, lncRNAs can affect the development, progression and metastasis of cancers
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