N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan–Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.

Purpose: Radioresistance is a vital obstacle for the prognosis of human nasopharyngeal carcinoma (NPC), but the underlying mechanism is still unknown. Here, we explored the role of the NRF2/KEAP1 pathway in radioresistance of NPC cell lines. Materials and Methods: We selected NPC cell lines CNE-1 and CNE-2, treated them with ionization, and subsequently determined the levels of NRF2, KEAP1, antioxidant enzymes, and ROS. We then evaluated the effect of NRF2 or KEAP1 inhibition on cell proliferation, colony formation, and radiosensitivity in CNE2 cells. Results: We discovered that the NRF2/KEAP1 signaling pathway can be activated by radiotherapy in NPC cells, while NRF2 knockdown enhances the sensitivity of CNE-2 cells to radiation treatment. In contrast, the silencing of KEAP1 inhibits the sensitivity of CNE-2 cells to radiation treatment. Conclusion: Our results suggest that NRF2/KEAP1 signaling may serve as an essential regulator of the radioresistance of NPC and may be applied as a novel therapeutic approach for the sensitization of NPC to radiation.

Background: Metastasis is the primary cause of recurrence and death in patients with papillary thyroid carcinoma (PTC). LncRNA ACTA2-AS1, a long non-coding RNA, acts as a tumor suppressor in multiple types of human malignancies, while the role of ACTA2-AS1 in PTC metastasis remains unclear. Methods: The ACTA2-AS1 expression in PTC tissues was analyzed. The sponged roles of ACTA2-AS1 via miR-4428/KLF9 axis were identified using starBase tool. The function of ACTA2-AS1 in PTC was performed with in vitro and in vivo experiments. The correlation between DNA methylation and mRNA expressions of these gene in the TCGA dataset was explored. Results: ACTA2-AS1 expression was downregulated in PTC tissues without metastasis and further decreased in PTC tissues with lymph node metastasis compared with that in normal tissues. Functionally, the overexpression of ACTA2-AS1 inhibited the growth, proliferation, and invasion of PTC cells, whereas its depletion exerted opposite effect. In vivo, ACTA2-AS1 expression inhibited PTC metastasis. Furthermore, ACTA2-AS1 acted as a competing endogenous RNA for miR-4428, thereby positively regulating the expression of miR-4428 target gene, KLF9. Finally, miR-4428 overexpression enhanced invasive potential of PTC cells and significantly weakened the effects of ACTA2-AS1 on promotion and inhibition of KLF9 expression as well as invasive ability of PTC cells, respectively. In the TCGA dataset, the methylation level of ACTA2-AS1 was significantly correlated with its mRNA expression (r = 0.21, p = 2.1 × e⁻⁶). Conclusions: Our findings demonstrate that ACTA2-AS1 functions as a tumor suppressor in PTC progression at least partly by regulating the miR-4428-dependent expression of KLF9. Graphical

Introduction: Head and neck squamous cell carcinoma (HNSCC) is a malignant neoplasm typically induced by alcohol and tobacco consumption, ranked the sixth most prevalent cancer globally. This study aimed to establish a cuproptosis-related lncRNA predictive model to assess the clinical significance in HNSCC patients.Methods: The Cancer Genome Atlas (TCGA) database was utilized to download cuproptosis-related genes, lncRNAs profiles, and selected clinical information of 482 HNSCC samples. Cuproptosis-related lncRNAs were analyzed by Pearson correlation method, with the least absolute shrinkage and selection operator (LASSO) and univariate/multivariate Cox analyses performed to establish the cuproptosis-related lncRNA predictive model. Subsequently, the time-dependent receiver operating characteristics (ROC) and Kaplan-Meier analysis were applied to assess its prediction ability, and the model was verified by a nomogram, univariate/multivariate Cox analysis, and calibration curves. Furthermore, the principal component analysis (PCA), immune analysis, and gene set enrichment analyses (GSEA) were performed, and the 50% inhibitory concentration (IC50) prediction in the risk groups was calculated. Furthermore, the expression of six cuproptosis-related lncRNAs in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR).Results: A total of 467 lncRNAs were screened as cuproptosis-associated lncRNAs in HNSCC tissues to establish an eight cuproptosis-related lncRNA prognostic signature consisting of AC024075.3, AC090587.2, AC116914.2, AL450384.2, CDKN2A-DT, FAM27E3, JPX, and LNC01089. For the high-risk group, the results demonstrated a satisfactory predicting performance with considerably worse overall survival (OS). Multivariate Cox regression confirmed that the risk score was a reliable predictive factor (95% CI: 1.089–1.208, hazard ratio =1.147), with the area of 1-, 3-, and 5-year OS under the ROC curve of 0.690, 0.78524, and 0.665, respectively. The differential analysis revealed that JPX was significantly upregulated in HNSCC tissues, while AC024075.3, AC090587.2, AC116914.2, AL450384.2, CDKN2A-DT were downregulated in HNSCC tissues by qRT-PCR assays. In addition, this gene signature was also associated with some immune-related pathways and immune cell infiltration and affected the anti-cancer immune response. Furthermore, Bexarotene, Bleomycin, Gemcitabine, etc., were identified as potential therapeutic compounds for HNSCC.Discussions: This novel cuproptosis-related lncRNAs prognostic signature could predict prognosis and help propose novel individual therapeutic targets for HNSCC.

Background: Cancer-associated fibroblasts (CAFs) play an essential role in tumorigenesis and development of cancers. Nevertheless, the specific molecular mechanism of tumorigenesis and development in Laryngeal squamous cell carcinoma (LSCC) still unknown. Methods: CAFs, CPFs and NFs were isolated and identified from laryngeal cancer, para-laryngeal cancer and normal tissues. Immunofluorescent staining, Rt-PCR and Western Blot were used to detect the expression of related proteins. Wound healing, migration, invasion and animal experiments were used to examine the ability of movement, migration, invasion and metastasis of LSCC. Results: ROCK1, was highly expressed in CAFs and CAFs enhanced LSCC metastasis in vivo and vitro, and downregulation of ROCK1 in CAFs inhibited the migration and invasion of LSCC cells. While increasing ROCK1 expression in NFs promoted the migration and invasion of LSCC cells. Further studies revealed that epithelial-mesenchymal transition (EMT) and JAK2/STAT3/ERK1/2 pathway might play an essential role in promoting metastasis of LSCC. In addition, inhibition activity of ROCK1 or JAK2/STAT3/ERK1/2 signal molecules significantly reduced EMT and metastasis. Conclusions: CAFs-derived ROCK1 via JAK2/STAT3/ERK1/2 axis mediated EMT to promote LSCC metastasis and targeting ROCK1 might provide a potential treatment strategy for LSCC.

We previously found that intravenous injection of extracellular vesicles (EVs) from human adipose tissue–derived stem cells (hADSC) could ameliorate allergic rhinitis (AR) in mice through immunomodulatory effects. In clinical trials, nasal delivery has been an attractive treatment for AR. We sought to determine whether there are differences in the therapeutic effects between caudal injection and their combination. We treated AR mice with ADSC-EVs via caudal vein, nasal cavity, or both. After treatment, the mice were re-sensitized and the indices of behavior, nasal mucosa morphology, and cytokine secretion of the mice under different modes of administration were calculated. The resultes show that tail vein, nasal, and combined administration could effectively relieve the inflammatory infiltration of the nasal mucosa of mice, reduce the secretion of IgE, IL-4, and other inflammatory factors, and alleviate the Th1/Th2 imbalance. Injection and nasal delivery, as well as their combination, effectively alleviated the symptoms of rhinitis in mice. Nasal administration has a better therapeutic effect when the inflammatory response is mild. It could be speculated that ADSC-EVs have excellent properties in the treatment of AR, and modes of administration can be selected for different stages of treatment in clinical therapy.