Abstract
Accumulating evidences highlight the critical roles of long noncoding RNAs (lncRNAs) in a variety of cancers. LncRNA PXN‐AS1‐L was previously shown to exert oncogenic roles in hepatocellular carcinoma. However, the expression, role, and molecular mechanism of PXN‐AS1‐L in nasopharyngeal carcinoma (NPC) malignancy remain unknown. Here, we determined that PXN‐AS1‐L is upregulated in NPC tissues and cell lines. Increased expression of PXN‐AS1‐L predicts worse prognosis of NPC patients. PXN‐AS1‐L overexpression promotes NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. PXN‐AS1‐L silencing suppresses NPC cell proliferation, migration, and invasion in vitro. Mechanistically, PXN‐AS1‐L directly interacts with SAPCD2 mRNA 3′‐untranslated region, prevents the binding of microRNAs‐AGO silencing complex to SAPCD2 mRNA, and upregulates the mRNA and protein level of SAPCD2. SAPCD2 is also increased in NPC tissues. The expression of SAPCD2 is significantly positively associated with that of PXN‐AS1‐L in NPC tissues. Gain‐of‐function and loss‐of‐function experiments demonstrated that SAPCD2 also promotes NPC cell proliferation, migration, and invasion. Furthermore, depletion of SAPCD2 significantly reverses the roles of PXN‐AS1‐L in promoting NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. In conclusion, lncRNA PXN‐AS1‐L is upregulated in NPC and promoted NPC malignancy by upregulating SAPCD2 via direct RNA‐RNA interaction.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the predominant head and neck cancers which derived from nasopharyngeal (NP) epithelium.[1]
Yuan et al recently reported that splicing factor MBNL3 modulated the alternative splicing of Long noncoding RNAs (lncRNAs) PXN‐AS1, which generated 2 different isoforms of PXN‐AS1.33 PXN‐AS1‐L is one of the isoforms which contains the exon 4 and has 863 nucleotides in length, and whereas PXN‐AS1‐S is another isoform which lacks the exon 4 and has 686 nucleotides in length.[33]
We focused our attention on lncRNA PXN‐AS1‐L
Summary
Nasopharyngeal carcinoma (NPC) is one of the predominant head and neck cancers which derived from nasopharyngeal (NP) epithelium.[1]. The expression pattern and roles of several lncRNAs in NPC have been studied.[8,25-30]. LOC284454 promotes NPC migration and invasion through regulating the Rho/Rac signaling pathway.[32]. The aberrant expression and roles of these lncRNAs have been reported, other lncRNAs may participate in the tumorigenesis and development of NPC. The expression, role, and action mechanism of PXN‐AS1‐L in NPC are unknown. We determined the expression pattern of PXN‐AS1‐L in NPC tissues and cell lines, analyzed the correlation between PXN‐AS1‐L expression levels and survival of NPC patients, and explored the roles of PXN‐AS1‐L in NPC cell proliferation, migration, and invasion, and in vivo NPC tumorigenesis. The molecular mechanisms responsible for the roles of PXN‐AS1‐L in NPC were investigated
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