Recently, circular RNAs have been shown to function as critical regulators of many human cancers. However, the circRNA mechanism in laryngeal squamous cell carcinoma (LSCC) remains elusive. Recent investigations using bioinformatics analysis revealed high expression of hsa_circ_0023305 in LSCC tissues compared to normal tissues. Furthermore, we discovered that hsa_circ_0023305 expression level was positively correlated to tumor/node/metastasis (TNM) stage as well as lymph node metastasis in LSCC. Moreover, higher hsa_circ_0023305 levels were correlated to poorer LSCC patient outcomes. Knockdown of hsa_circ_0023305 significantly inhibited LSCC cell proliferation, invasion, and migration abilities. Our team validated that hsa_circ_0023305 functioned as a miR‐218‐5p sponge from a mechanistic perspective, targeting the melastatin‐related transient receptor potential 7 (TRPM7) in LSCC cells. TRPM7 regulates a nonselective cation channel and promotes cancer proliferation and metastasis. Our data demonstrated that miR‐218‐5p was downregulated in LSCC and that miR‐218‐5p upregulation repressed LSCC proliferation and invasion both in vivo and in vitro. Additionally, we found that hsa_circ_0023305‐mediated upregulation of TRPM7 inhibited miR‐218‐5p and contributed to LSCC migration, proliferation, and invasion. In summary, these data propose a new mechanism by which the hsa_circ_0023305/miR‐218‐5p/TRPM7 network enhances LSCC progression.

The development of nasal inverted papilloma (NIP) is closely related to human papillomavirus (HPV) infection. Previous studies indicated that HPV11 shows the highest expression in NIP tissues. However, the mechanisms following its integration into host DNA require further clarification. In this study, high-throughput sequencing was employed to identify the HPV integration site KDM4A in HPV-positive specimens. The HPV11E6/E7 overexpression model was established in human nasal mucosal epithelial cells (HNE-pC), and the KDM4A gene was knocked out using CRISPR/Cas9 technology. Cell proliferation was assessed via CCK-8, colony formation, and EdU assays, while cell migration was evaluated through Transwell and wound healing assays. qRT-PCR and Western blot were used not only to analyze mRNA and protein expression in cells after HPV11E6/E7 overexpression and knockout of KDM4A but also to study the effect of the polarization of macrophages. A subcutaneous tumor model in nude mice validated the effects on proliferation and KDM4A knockout in vivo, with macrophage polarization types assessed via immunofluorescence staining. Results showed that HPV11E6/E7 overexpression significantly enhanced nasal epithelial cell proliferation and migration, along with promoting M1 macrophage polarization. Knockout of KDM4A inhibited these effects and delayed the progression of macrophages toward M1 polarization. Our findings suggest that low-risk HPV11 can drive the proliferation of nasal mucosa and regulate M1 macrophage polarization via KDM4A, potentially contributing to NIP pathogenesis. Targeting inhibition of KDM4A expression may represent a viable therapeutic strategy for HPV-positive NIP.

Background: Circular RNAs (circRNAs) belong to a class of covalently closed single stranded RNAs that have been implicated in cancer progression. Former investigations showed that hsa-circ-0013561 is abnormally expressed in head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of hsa-circ-0013561 during the progress of HNSCC still unclear. Methods: Present study applied FISH and qRT-PCR to examine hsa-circ-0013561 expression in HNSCC cells and tissue samples. Dual-luciferase reporter assay was employed to identify downstream targets of hsa-circ-0013561. Transwell migration, 5-ethynyl-2′-deoxyuridine incorporation, CCK8 and colony formation assays were utilized to test cell migration and proliferation. A mouse tumor xenograft model was utilized to determine the hsa-circ-0013561 roles in HNSCC progression and metastasis in vivo. Results: We found that hsa-circ-0013561 was upregulated in HNSCC tissue samples. hsa-circ-0013561 downregulation inhibited HNSCC cell proliferation and migration to promote apoptosis and G1 cell cycle arrest. The dual-luciferase reporter assay revealed that miR-7-5p and PDK3 are hsa-circ-0013561 downstream targets. PDK3 overexpression or miR-7-5p suppression reversed the hsa-circ-0013561-induced silencing effects on HNSCC cell proliferation and migration. PDK3 overexpression reversed miR-7-5p-induced effects on HNSCC cell proliferation and migration. Conclusion: The findings suggest that hsa-circ-0013561 downregulation inhibits HNSCC metastasis and progression through PDK3 expression and miR-7-5p binding modulation.

Nasopharyngeal Carcinoma (NPC) is a malignancy of epithelium of epithelium of the nasopharynx, with the highest incidence of otolaryngeal malignancies. A growing number of studies confirm that Circular RNA (circRNA) plays an important role in tumor development, including Hsa_circ_0013561. This study aims to elucidate the process and mechanism of NPC regulation hsa_circ_0013561. In this study, circRNA expression nodes and subcellular localization in NPC tissues were analyzed by fluorescence in situ hybridization. The expression of hsa_circ_0013561 in NPC cells was further clarified by RT-qPCR. At the same time, the lentivirus vector interfered by hsa_circ_0013561 was constructed and transfected. The cell proliferation was detected by CCK-8 method, EdU assay and plate cloning assay. The cell cycle and apoptosis were detected by flow cytometry, and the cell migration ability was detected by wound healing assay and Transwell assay. Western blotting examined the expression of apoptosis, Epithelial-Mesenchymal Transition (EMT)-associated proteins, and Janus Kinase/Signal Transductor and Activator of Transcription (JAK/STAT) signaling pathway-related proteins. The results showed that the expression of hsa_circ_0013561 in NPC samples was significantly upregulated and hsa_circ_0013561 localized in the cytoplasm. After down-regulating hsa_circ_0013561 expression, it significantly inhibited the proliferation and metastasis ability of NPC, inhibited EMT progression, and promoted apoptosis. Further studies showed that interference hsa_circ_0013561 significantly inhibited JAK2/STAT3 signaling pathway activation and induced the expression of apoptosis-related proteins. In summary, we found that hsa_circ_0013561 is a pro-tumor circRNA in NPC, which can reduce the activation of JAK2/STAT3 pathway by knocking down hsa_circ_0013561, thereby slowing down the malignant progression of NPC. OXFORD CENTRE FOR EVIDENCE-BASED MEDICINE 2011 LEVELS OF EVIDENCE: Level 4.

Nasal mucosal epithelial hyperplasia can cause nasal hyperplastic diseases, more studies have confirmed that different subtypes of HPV infection play a significant role in nasal proliferative diseases, especially nasal inverted papilloma (NIP). This study aims to elucidate the role and mechanism of the HPV11 subtype in regulating nasal epithelial hyperplasia. In our previous study, the expression of HPV infection in NIP was analyzed by Flow-through hybridization and gene chip (HybridMax), with the highest expression rate observed for the HPV11 subtype. Therefore, we aimed to overexpress HPV11E6/E7 in nasal mucosal epithelial cells (HNEpC) to verify the regulatory role and mechanism of HPV11 in nasal epithelial hyperplasia at the cellular level. In this manuscript, we constructed a lentiviral vector overexpressing HPV11E6/E7 and transfected it into HNEpC. We used HNEpC as the control group and HPV11E6/E7-overexpressing cells as the experimental group. Cell proliferation was assessed using CCK-8, EdU, and colony formation assays. Cell migration ability was evaluated by wound healing and Transwell assays. Protein expression levels related to apoptosis, epithelial–mesenchymal transition (EMT), and the JAK2/STAT3 pathway were analyzed by western blot. The results showed that overexpression of HPV11E6/E7 significantly increased the proliferation and migration of nasal epithelial cells, promoted the progression of EMT, and inhibited cell apoptosis. Further verification showed that the overexpression of HPV11E6/E7 significantly promoted the activation of the JAK2/STAT3 signaling pathway. In summary, we found that low-risk subtype HPV11 promotes nasal mucosal epithelial hyperplasia and malignant progression by increasing activation of the JAK2/STAT3 pathway. The JAK2/STAT3 pathway has been prioritized due to its established role in promoting cell proliferation and EMT in HPV-related diseases.

Objective: This study aims to analyze the genes that influence PTC progression and investigate the role of MAPK13 in PTC. Methods: Differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO): GSE3467, GSE3678, GSE33630, and GSE58545 were analyzed between PTC and normal thyroid tissues. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were performed on the DEGs using The Cancer Genome Atlas (TGCA) Program data. MAPK13 was subsequently identified as promoting progression in PTC. The association between MAPK13 expression and clinicopathological features was analyzed using data from public database and the collected cohort. The CCK-8 assay, EdU assay, wound healing assay, transwell assay, flow cytometry, GSEA enrichment analysis, and xenograft model were used to investigate the function of MAPK13 in PTC. Results: Higher expression of MAPK13 was associated with poorer progression-free survival, higher tumor pathologic stage, extrathyroidal extension, lymph node metastasis, multifocal tumors, American Thyroid Association (ATA) stratification system level, and BRAFV600E mutation. Overexpression of MAPK13 significantly promoted cell proliferation, migration, and invasion, and inhibited apoptosis of PTC. Knockdown of MAPK13 significantly inhibited cell proliferation, migration, and invasion, and promoted apoptosis of PTC. Epithelial-mesenchymal transition (EMT) was significantly enriched in GSEA analysis. Higher MAPK13 expression was related to higher N-cadherin and lower E-cadherin expression. Knockdown of MAPK13 significantly prevented tumor growth in vivo. Conclusion: MAPK13 promotes the malignant biological behavior of PTC cells and is associated with EMT. MAPK13 may be a potential biomarker for treatment.