Search

Background: In recent years, the development of high-throughput sequencing technology has promoted the rapid development of circRNA-related research. Studies have found that circRNA plays a key role in a variety of tumors, but few people study the role of circRNA in nasopharyngeal carcinoma. Under comprehensive treatments, the 5-year survival rate can reach about 70%, but some patients still have distant metastases or recurrences after treatment. Therefore, it is very important to study the molecular mechanisms of the proliferation and invasion of nasopharyngeal carcinoma., Methods: QRT-PCR was applied to detect the relative expression level of circFOXM1 in NPC and nasopharyngeal epithelial cell lines. We knocked down circFOXM1 and studied the influence of circFOXM1 on NPC cells. Nuclear and cytoplasmic RNA isolation experiments, fluorescence in situ hybridization (FISH), bioinformatics analysis, the dual-luciferase reporter experiment, Western Blot, and other experiments were conducted to verify the relationships among circFOXM1, miR-136-5p, and SMAD2. We collected clinical NPC samples to prove the effect of circFOXM1 on the prognosis and treatment of NPC., Results: In this study, we found that circFOXM1 is highly expressed in nasopharyngeal carcinoma tissue cells compared with adjacent normal tissues and is related to the staging of nasopharyngeal carcinoma. High expression of circFOXM1 indicates a poor prognosis for nasopharyngeal carcinoma. Knockdown of CircFOXM1 inhibited the proliferation and invasion of nasopharyngeal carcinoma cells., Conclusion: CircFOXM1 promotes the malignant proliferation of nasopharyngeal carcinoma cells by regulating the miR-136-5p-SMAD2 axis., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Nasopharyngeal carcinoma (NPC) is known for its potential to progress to the lymph nodes and distant metastases at an early stage. As an important regulator in tumorigenesis biological processes, the functions of lncRNA in NPC tumor development remain largely unclear. In this research, the expression of EPB41L4A-AS2 in NPC tissues and cells was analyzed via real-time quantitative polymerase chain reaction (qRT-PCR). CCK8, colony formation, and EDU experiments were used to determine the viability of NPC cells. Transwell and wound healing assays were performed to test NPC cell migration and invasion. RNA pull-down and mass spectrometry analysis were used to identify potential binding proteins. Then, a popliteal lymph node metastasis model was established to test NPC metastasis. EPB41L4A-AS2 is repressed by transforming growth factor-beta, which is downregulated in NPC cells and tissue. It is associated with the presence of distant metastasis and adverse outcomes. The univariate and multivariate survival assays confirmed that EPB41L4A-AS2 expression was an independent predictor of progression-free survival (PFS) in patients with NPC. Biological analyses showed that overexpression of EPB41L4A-AS2 reduced the metastasis and invasion of NPC in vitro and in vivo , but had no significant effect on cell proliferation. Mechanistically, in the nucleus we identified that EPB41L4A-AS2 relies on binding to YBX1 to reduce the stability of Snail mRNA to enhance the expression of E-cadherin and reverse the progression of epithelial-to-mesenchymal transition (EMT). In the cytoplasm, we found that EPB41L4A-AS2 blocked the invasion and migration of NPC cells by promoting LATS2 expression via sponging miR-107. In a whole, the findings of this study help to further understand the metastasis mechanism of NPC and could help in the prevention and treatment of NPC metastasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Accumulating evidences indicate that circular RNAs (circRNAs), a subclass of noncoding RNAs, play important role in regulating gene expression in eukaryotes. Hsa_circ_0046263 (circ-0046263) was found aberrantly expressed in nasopharyngeal carcinoma (NPC), but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, RNase R assay, and nucleic acid electrophoresis were conducted to verify the identification of circ-0046263. Nuclear separation and fluorescence in situ hybridization (FISH) assays were used to determine the localization of circ-004263. Dual luciferase reporter and RNA immunoprecipitation (RIP) were employed to confirm the binding of circ-0046263 with miR-133a-5p. Colony formation, proliferation, wound healing, transwell, western blot, and in vivo tumor growth and metastasis assays were performed to assess the roles of circ-0046263, miR-133a-5p, IGFBP3 and their interactions in NPC cells. Circ-0046263 was upregulated in both NPC cell lines and tissues. The in vitro functional studies revealed that knockdown of circ-0046263 inhibited the proliferation, invasion, and migration of NPC cells, whereas its overexpression produced the opposite result. In vivo experiments indicated that knockdown or overexpression of circ-0046263 attenuated or promoted tumor growth and metastasis, respectively. Mechanistically, circ-0046263 could act as a miRNA sponge to absorb miR-133a-5p and upregulate the expression of miRNA downstream target IGFBP3. In addition, miR-133a-5p inhibition or IGFBP3 overexpression could rescue the malignant behavior induced by circ-0046263 silencing. Finally, circ-0046263 plays a tumor-promoting role in NPC to enhance malignant behavior through the miR-133a-5p/IGFBP3 axis, which could be a potential target for NPC therapy.

Background: Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors. Long noncoding RNAs play critical roles in tumorigenesis., Methods: Real-time quantitative PCR arrays were used to evaluate the expression levels of cytoskeleton regulator RNA (CYTOR) in NPC tissues and cells. Cell counting kit-8 and colony formation analyses were used to test the NPC cell viability, while wound healing and transwell assays were employed to detect cell invasion and migration ability. Luciferase reporter assay and Western blot analyses were employed to explore the relationships among CYTOR, miR-613, and ANXA2., Results: We found that CYTOR expression was elevated both in NPC tissues and cells. Functional assays revealed that CYTOR promoted the invasion and migration of NPC cells. The established spontaneous lymph node metastasis model also confirmed that CYTOR promoted NPC cell metastasis in vivo. Mechanically, we found that the subcellular localization of CYTOR mostly occurred in the cell cytoplasm. Luciferase reporter and RIP assays confirmed that CYTOR functioned as the molecular sponge of miR-613. Subsequent experiments confirmed that ANXA2 was directly targeted by miR-613. Gain- and loss-of-function studies further confirmed that CYTOR induced the upregulation of ANXA2 by competitively binding to miR-613, thus leading to NPC metastasis., Conclusion: Our results highlight the importance of CYTOR in NPC development and provide new insights into potential therapeutic targets for NPC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background and purpose: Circular RNA (circRNA) plays an important regulatory role in the development of a variety of tumors. However, the abnormal expression and biological function of circRNA in nasopharyngeal carcinoma remain unclear. This study aimed to explore the effect of hsa_circ_0012779 on the biological behavior of nasopharyngeal carcinoma cells and its molecular mechanism. Methods: The expression of hsa_circ_0012779 in human immortalized nasopharyngeal epithelial cell line NP69 and nasopharyngeal carcinoma cell lines CNE2, 5-8F, HNE1 and SUNE1 was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Cell counting kit-8 (CCK-8) assay and transwell invasion assay were used to detect the effect of hsa_circ_0012779 on the proliferation and invasion ability of nasopharyngeal carcinoma cells. The protein level of ELAV like protein 1 (ELAVL1) in NPC cells with hsa_circ_0012779 knockdown was detected by Western blot. The binding of hsa_circ_0012779 and ELAVL1 was verified by RNA pull-down assay. Results: hsa_circ_0012779 was highly expressed in nasopharyngeal carcinoma tissues and cells. Knockdown hsa_circ_0012779 could inhibit the proliferation and invasion of nasopharyngeal carcinoma cells. hsa_circ_0012779 bound to RNA-binding protein ELAVL1 to promote its expression and colocalization in cytoplasm. In the meanwhile, the effect of knockdown hsa_circ_0012779 on nasopharyngeal carcinoma cells could be reversed by the overexpression of ELAVL1. Conclusion: hsa_circ_0012779 promote the expression of ELAVL1 and thus promote the proliferation and invasion of nasopharyngeal carcinoma, and influence the occurrence and development of nasopharyngeal carcinoma.

The long non‐coding RNA (lncRNA)–microRNA (miRNA) interaction network plays a crucial part in the pathogenesis of nasopharyngeal carcinoma (NPC). Here, we discovered a relationship between LINC01376 and miR‐4757 in NPC tumor development. First, LINC01376 was abnormally overexpressed in NPC tissues and cells, and its elevated expression was associated with advanced clinical stage and shorter distant metastasis‐free survival time. Moreover, biological experiments showed that LINC01376 facilitated the proliferative, invasive, and migratory abilities of NPC cells in vitro and in vivo. Mechanistically, bioinformatics and RT‐qPCR assays revealed that LINC01376 knockdown upregulated the expression level of downstream miR‐4757, including miR‐4757 primary transcript (pri‐miR‐4757) and mature miR‐4757. Furthermore, LINC01376 competitively sponged the transcription factor SP1 and reduced its enrichment in the upstream promoter region of miR‐4757 to repress miR‐4757 expression. Finally, insulin‐like growth factor 1(IGF1) was identified as the target of miR‐4757. Rescue experiments indicated that LINC01376 accelerated NPC cell proliferation, migration, and invasion through the miR‐4757‐5p/IGF1 axis. In conclusion, the SP1/miR‐4757/IGF1 axis, which is regulated by LINC01376 in NPC deterioration and metastasis, is expected to provide new insights into the molecular mechanism of NPC carcinogenesis. [ABSTRACT FROM AUTHOR]