Affiliation:
1. Department of Respiratory, Gaoxin Branch of The First Affiliated Hospital of Nanchang University, Nanchang,
P.R. China
2. Department of Oncology, Gaoxin Branch of The First Affiliated Hospital of Nanchang University,
Nanchang, P.R. China
Abstract
Background and Objective:
Understanding the regulatory mechanisms involving neuronatin
(NNAT) in non-small cell lung cancer (NSCLC) is an ongoing challenge. This study aimed
to elucidate the impact of NNAT knockdown on NSCLC by employing both in vitro and in vivo approaches.
Methods:
To investigate the role of NNAT, its expression was silenced in NSCLC cell lines A549
and H226. Subsequently, various parameters, including cell proliferation, invasion, migration, and
apoptosis, were assessed. Additionally, cell-derived xenograft models were established to evaluate
the effect of NNAT knockdown on tumor growth. The expression of key molecules, including cyclin
D1, B-cell leukemia/lymphoma 2 (Bcl-2), p65, matrix metalloproteinase (MMP) 2, and nerve
growth factor (NGF) were examined both in vitro and in vivo. Nerve fiber density within tumor tissues
was analyzed using silver staining.
Results:
Upon NNAT knockdown, a remarkable reduction in NSCLC cell proliferation, invasion,
and migration was observed, accompanied by elevated levels of apoptosis. Furthermore, the expression
of cyclin D1, Bcl-2, MMP2, and phosphorylated p65 (p-p65) showed significant downregulation.
In vivo, NNAT knockdown led to substantial inhibition of tumor growth and a concurrent
decrease in cyclinD1, Bcl-2, MMP2, and p-p65 expression within tumor tissues. Importantly,
NNAT knockdown also led to a decrease in nerve fiber density and downregulation of NGF expression
within the xenograft tumor tissues.
Conclusion:
Collectively, these findings suggest that neuronatin plays a pivotal role in driving NSCLC
progression, potentially through the activation of the nuclear factor-kappa B signaling cascade.
Additionally, neuronatin may contribute to the modulation of tumor microenvironment innervation
in NSCLC. Targeting neuronatin inhibition emerges as a promising strategy for potential
anti-NSCLC therapeutic intervention.
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
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