Long noncoding RNA PXN‐AS1‐L promotes the malignancy of nasopharyngeal carcinoma cells via upregulation of SAPCD2

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.

Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway

“…The INSIG1 metabolic regulator, whose expression is downregulated in DHA-treated cells (see above), may also play a regulatory role during the G0/G1 transition of cell growth [69]. Genes that are involved in the mitotic process, such as ASPM and SAPCD2 may also play a role in the positive regulation of cell proliferation, and tumor cell growth [70][71][72][73][74], the DHA-induced decrease of their expression is then consistent with the antiproliferative effect of DHA.…”

KIF9‑AS1 promotes nasopharyngeal carcinoma progression by suppressing miR‑16

“…For example, lncRNA ZFAS1 was reported to accelerate the proliferation of NPC cells via the activation of the PI3K/AKT signaling pathway ( 25 ). Jia et al ( 15 ) also demonstrated that lncRNA PXN-AS1-L promoted the proliferation, migration and invasion of NPC cells through upregulating the expression levels of suppressor APC domain-containing protein 2. Therefore, determining the involvement of cancer-specific lncRNAs may prove beneficial for identifying novel targets for anticancer treatment.…”

“…MicroRNAs (miRNAs/miRs) are a family of small non-coding RNAs of ~22 nucleotides in length, which regulate gene expression by complementary binding or complex mechanisms ( 13 – 15 ). miRNAs have been reported to be aberrantly expressed in NPC, where they have been found to regulate NPC cell proliferation, invasion and metastasis ( 16 ).…”

Diagnostic and Prognostic Indications of Nasopharyngeal Carcinoma

“…Other known oncogenic lncRNAs involved in NPC include HOTTIP, HOTAIR, ROR, XIST, HNF1A-AS, DRAIC, NPCCAT1, ANRIL, H19, LINC01385, LINC01503, CASC15, PXN-AS1-L, LINC00460, and UCA1, which involve in increasing cell proliferation, migration, invasion, and metastasis [106][107][108][109][110][111][112][113][114][115][116][117][118][119][120]. High expressions of LINC00319, LINC01503, HOTTIP, PXN-AS1-L, ANRIL, HOTAIR, LINC01385, and XIST are associated with poor prognosis and short overall survival in NPC [106,107,109,113,115,117,120,121]. LncRNAs, LINC00346, and ROR play a critical functional role in chemoresistance, particularly cisplastin therapy [108,122], while MALAT1, PVT1, and NEAT1 play a major role in radioresistance [105,123,124] (Table 3).…”

“…NPC primary biopsy EBV-LMP1 (62.5%) [24] EBV-BARF1 (13.3%) [24] miR-141 [136] lncRNA PVT1 (64%) [105] lncRNA NPCCAT1 [112] lncRNA CASC15 [116] lncRNA PXN-AS1-L [117] lncRNA HOTTIP [106] lncRNA LINC00346 [122] lncRNA LINC01503 [115] lncRNA LINC00460 [118] lncRNA UCA1 [119] lncRNA ANRIL [113] lncRNA H19 [114] lncRNA MALAT1 [123] lncRNA NEAT1 [124] lncRNA LINC01385 [120] lncRNA HNF1A-AS [110]…”