Silencing of long noncoding RNA SRRM2-AS exerts suppressive effects on angiogenesis
in nasopharyngeal carcinoma via activating MYLK-mediated cGMP-PKG signaling pathway
Long noncoding RNAs (lncRNAs) play a crucial role in several malignances, involving
nasopharyngeal carcinoma (NPC), a heterogeneous disease. This study investigated mechanism
of serine/arginine repetitive matrix protein 2-alternative splicing (SRRM2-AS) in
NPC cell proliferation, differentiation, and angiogenesis. Initially, differentially
expressed lncRNAs were screened out via microarray analysis. Vascular endothelial
growth factor (VEGF) protein positive rate and microvessel density (MVD) were determined
in NPC and adjacent tissues. NPC CNE-2 cells were treated with a series of vector
and small interfering RNA to explore the effect of SRRM2-AS in NPC. The target relationship
between myosin light chain kinase (MYLK) and SRRM2-AS was verified. Levels of SRRM2-AS,
MYLK, cGMP, PKG, VEGF, PCNA, Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X
protein (Bax), and Caspase 3 were determined after transfection. Finally, the effect
of SRRM2-AS on cell proliferation, colony formation, angiogenesis, cell cycle, and
apoptosis in NPC was evaluated. SRRM2-AS was highly expressed and MYLK was poorly
expressed in NPC tissues. VEGF protein positive rate and MVD were elevated in NPC
tissues. MYLK was confirmed to be a target gene of SRRM2-AS. Silencing of SRRM2-AS
elevated levels of MYLK, cGMP, PKG, Bax, and Caspase 3, but decreased levels of VEGF,
PCNA, Ki-67, and Bcl-2. Especially, silencing of SRRM2-AS suppressed cell proliferation,
colony formation and angiogenesis, blocked cell cycle, and enhanced cell apoptosis
in NPC. Our results suggested that silencing of SRRM2-AS protected against angiogenesis
of NPC cells by upregulating MYLK and activating the cGMP-PKG signaling pathway, which
provides a new target for NPC treatment.