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Objectives: Circular RNAs (circRNAs), with their multilevel and versatile regulation, have emerged as promising targets for treating complex and heterogeneous malignancies such as oral squamous cell carcinoma (OSCC). It is crucial to explore the function of key circRNAs and elucidate the underlying mechanisms to establish an effective in vivo delivery system to better utilize circRNAs as cancer treatment strategies. Materials and Methods: circRNA (circ‐OCAC) was identified as significantly downregulated in tumor samples compared to paracancerous tissues by RNA‐seq analysis of eight pairs of OSCC tissues. Functional experiments of circ‐OCAC were performed both in vitro and in vivo. The interactions between circ‐OCAC and miR‐411‐5p were clarified by RNA pull down and RNA immunoprecipitation (RIP) assays. Results: We observed that circ‐OCAC inhibits OSCC growth and metastasis by blocking the PI3K/Akt signaling pathway. To translate this observation in vivo, a pH‐responsive nanoparticle (pNP) was developed to target circ‐OCAC. Our results confirmed the advantages of the pNP‐circ‐OCAC system: high tumor enrichment capacity and good biosafety, which resulted in a significantly enhanced antitumor effect. Conclusions: This study demonstrated that targeting circ‐OCAC serves as a promising potential therapeutic strategy for OSCC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) in oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) play a pivotal role in modulating intercellular communications between tumor cells and other cells in the microenvironment, thereby influencing tumor progression and the efficacy of therapeutic interventions. However, a comprehensive inventory of these secretory miRNAs in sEVs and their biological and clinical implications remains elusive. This study aims to profile the miRNA content of OSCC cell line sEVs and computationally elucidate their biological and clinical relevance. We conducted miRNA sequencing to compare the miRNA profiles of OSCC cells and their corresponding sEVs. Our motif enrichment analysis identified specific sorting motifs that are implicated in either cellular retention or preferential sEV secretion. Target cell analysis suggested that the sEV miRNAs potentially interact with various immune cell types, including natural killer cells and dendritic cells. Additionally, we explored the clinical relevance of these miRNAs by correlating their expression levels with TNM stages and patient survival outcomes. Intriguingly, our findings revealed that a distinct sEV miRNA signature is associated with lymph node metastasis and poorer survival in patients in TCGA-HNSC dataset. Collectively, this research furthers our understanding of the miRNA sorting mechanisms in OSCC and underscores their clinical implications. [ABSTRACT FROM AUTHOR]

Background. Head and neck squamous cell carcinoma (HNSCC) is a growing concern worldwide, due to its poor prognosis, low responsiveness to treatment, and drug resistance. Since immunotherapy effectively improves HNSCC patients' survival status, it is important to continuously explore new immune-related predictive factors to accurately predict the immune landscape and clinical outcomes of individuals suffering from HNSCC. Methods. The HNSCC transcriptome profiling of RNA-sequencing data was retrieved from TCGA database, and the microarray of GSE27020 was obtained from the GEO database for validation. The differentially expressed genes (DEGs) between HNSCC and normal samples were identified by multiple test corrections in TCGA database. The univariate and multivariate Cox analyses were performed to identify proper immune-related genes (IRGs) to construct a risk model. The Cox regression coefficient was employed for calculation of the risk score (RS) of IRG signature. The median value of RS was utilized as a basis to classify individuals with HNSCC into high- and low-risk groups. The Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves were employed for the identification of the prognostic significance and precision of the IRG signature. The signature was also evaluated based on clinical variables, predictive nomogram, mutation analysis, infiltrating immune cells, immune-related pathways, and chemotherapeutic efficacy. The protein-protein interaction (PPI) network and functional enrichment pathway investigations were utilized to explore possible potential molecular mechanisms. Finally, the hub gene's differential mRNA expression levels were evaluated by means of the Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA) was utilized for the validation of their translational levels. Results. Collectively, 1593 DEGs between HNSCC and normal samples were identified, of which 136 IRGs were differentially expressed. Then, the 136 immune-related DEGs were mostly enriched in the cytokine-related signaling pathways by GO and KEGG analyses. After that, a valuable signature based on seven genes (DKK1, GAST, IGHM, IL12RB2, SLURP1, STC2, and TNFRSF4) was designed. The HNSCC patients into the low-risk group and the high-risk group were divided by using the median RS; the HNSCC patients in the high-risk group had a worse survival than those in the low-risk group. The risk signature was verified to be an independent predictive marker for HNSCC patients. Meanwhile, the RS had the largest contribution to survival of these patients based on the predictive nomogram. In addition, the low-risk HNSCC patients exhibited significantly enriched immune cells, along with an association with high chemosensitivity. Conclusion. The constructed gene signature can independently function as a predictive indicator for the clinical features of HNSCC patients. The low-risk HNSCC subjects might benefit from immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: As a novel class of endogenous ncRNAs, Circular RNAs (circRNAs) have been verified to be involved in the carcinogenesis and tumor progression. OBJECTIVE: This study aimed to investigate the potential function of a candidate circRNA hsa_circ_0036988 in oral squamous cell carcinoma (OSCC). METHODS: The altered expression of hsa_circ_0036988 was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in OSCC samples and OSCC cell lines. The associations between the levels of hsa_circ_0036988 and the clinicopathological features were statistically analysed. The function of hsa_circ_0036988 in OSCC were evaluated via a series of in vitro experiments by using constructed plasmids or siRNA. Western blotting assays were conducted to evaluate changes in protein expression levels. RESULTS: Hsa_circ_0036988 was significantly downregulated in OSCC tissues compared with adjacent normal tissues. While low expression of hsa_circ_0036988 was highly correlated with lymph nodes metastasis. Overexpression or knockdown of hsa_circ_0036988 significantly affected the proliferation, migration and invasion of OSCC cells. Furthermore, the altered expression of hsa_circ_0036988 have an impact on the epithelial-to-mesenchymal transition (EMT)-related protein expression levels. CONCLUSIONS: Our findings indicated that hsa_circ_0036988 may affect cell proliferation, migration and invasion by regulating EMT progress, which might provide a therapeutic strategy for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) has been discovered and demonstrated to have significant function in multiple cancers. Nevertheless, how it participates in the progression of oral squamous cell carcinoma (OSCC) and its potential regulatory system are still unclear.Methods: RT-qPCR detected the expression of SNHG15, miR-188-5p, and DAAM1. RNA pull down, RT-qPCR, and bioinformatics were used for finding and selecting downstream targets of SNHG15.Results: SNHG15 presented a high expression in OSCC cells. Moreover, inhibition of SNHG15 exhibited repressive influence on proliferative, migrated, and invasive abilities but induce apoptosis of OSCC cells. Through the search of bioinformatics and RNA pull down assays, we confirmed that miR-188-5p was one target of SNHG15 in OSCC cells. Additionally, miR-188-5p could hamper the growth of OSCC cells. Moreover, it was manifested that DAAM1 was down-regulated by miR-188-5p. DAAM1 was up-regulated in OSCC cells. Furthermore, it exerted oncogenic function in the course of OSCC. Eventually, overexpression of DAAM1 offsets the effects of down-regulation of SNHG15 on the development of OSCC.Conclusion: To summarize, our study certified that SNHG15 contributed to the process of OSCC via sponging miR-188-5p to elevate DAAM1 expression. SNHG15 might offer novel sight to improve the results of treatment for OSCC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC), the most common oral cancer, damages oral epithelial cells after the accumulation of multiple genetic mutations. Although emerging evidence supports the key role of circular RNAs (circRNAs) in various malignancies, the clinical value and function of circRNAs in OSCC remain unclear. In this study, patients with OSCC (n = 8) and controls (n = 8) were compared using high‐throughput sequencing and microarray circRNA expression profiles. The circRNA hsa_circ_0007059 was downregulated in OSCC. Subsequently, hsa_circ_0007059 levels in OSCC tissues and cell lines were assessed by quantitative reverse‐transcription chain reaction. Loss‐of‐function and gain‐of‐function experiments were performed to determine whether hsa_circ_0007059 affects malignant behavior in SCC15 and CAL27 cells. Importantly, hsa_circ_0007059 upregulation suppressed cell growth, migration, and invasion, facilitating apoptosis of these cells. Furthermore, nude mouse tumor formation was assessed to validate the tumor‐suppressive role of hsa_circ_0007059 in vivo. Finally, hsa_circ_0007059 was determined to alter cell growth via AKT/mTOR signaling, representing a potential prognostic/therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown.Methods: By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of circRNA hsa_circ_0005379 on OSCC tissues and cell lines was monitored by qRT-PCR, Transwell assay, flow cytometry, and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival.Results: We found that circRNA hsa_circ_0005379 expression is significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of hsa_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro and suppresses OSCC growth in nude mice in vivo. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of the epidermal growth factor receptor (EGFR) pathway. Furthermore, we found that high expression of hsa_circ_0005379 could significantly enhance the sensitivity of OSCC to the cetuximab drug.Conclusions: Our findings provide evidence that hsa_circ_0005379 regulates OSCC malignancy and may be a new therapeutic target for OSCC treatment. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy that exhibits high incidence worldwide. In diverse human cancers, the long non‐coding RNA (lncRNA) highly up‐regulated in liver cancer (HULC) is aberrantly expressed, but how HULC affects OSCC development and progression has remained mostly unknown. We report that HULC was abnormally up‐regulated in oral cancer tissues and OSCC cell lines, and that suppression of HULC expression in OSCC cells not only inhibited the proliferation, drug tolerance, migration and invasion of the cancer cells, but also increased their apoptosis rate. Notably, in a mouse xenograft model, HULC depletion reduced tumorigenicity and inhibited the epithelial‐to‐mesenchymal transition process. Collectively, our findings reveal a crucial role of the lncRNA HULC in regulating oral cancer carcinogenesis and tumour progression, and thus suggest that HULC could serve as a novel therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

Exp Ther Med 25:92, 2023; DOI: 10.3892/etm.2023.11790 Subsequently to the publication of the above article, the authors have realized that, for the scratch-wound healing assay experiments shown on p. 6 and 7, the same image had inadvertently been selected to show the results of the "24 h observation" experiments presented in Figs. (A) GCV treatment inhibited HSC-3 mVenus-TK but not HSC-3 mVenus cell migration during the 0-24 h period. After taking the scratch images, cells were treated with 25 µM GCV for a further 24 h, then the healing images were captured (scale bar, 100 µm). [Extracted from the article]

Objective. Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region. The circular RNA (circRNA) is known to serve an important role in the carcinogenesis of different types of cancer. However, the circRNA role of OSCC remains unclear. Methods. 8 pairs of OSCC tissues and adjacent normal tissues were obtained to detect circRNAs expression by high-throughput sequencing, and 45 pairs of OSCC tissues were selected to verify the differentially significant circRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). To further investigate the role of hsa_circ_0008309, the circRNA-microRNA (miR)-mRNA network was predicted using bioinformatics databases. The expression levels of hsa_circ_0008309, miR-1290, miR-136-5P, and miR-382-5P in SCC-15 and CAL27 cell lines were detected by RT-qPCR. Western blotting was performed to detect the protein level of Ataxin 1 (ATXN1). Results. The high-throughput sequencing results demonstrated that circRNAs were abundantly expressed in OSCC, and 16 circRNAs were significantly differentially expressed. Hsa_circ_0008309 was significantly downregulated in 45 pairs of OSCC tissue samples and was statistically correlated with pathological differentiation. The bioinformatics databases suggested that hsa_circ_0008309 could combine with miR-1290, miR-136-5P, and miR-382-5P, respectively, to regulate the expression of ATXN1. It was subsequently identified that hsa_circ_0008309 may inhibit miR-136-5P and miR-382-5P expression and increase ATXN1 expression in the OSCC cell lines. Conclusion. In summary, the results of the present study revealed that OSCC tissues have abundant circRNAs and, to the best of our knowledge, we firstly explore the regulatory role of the hsa_circ_0008309-miR-136-5P/hsa-miR-382-5P-ATXN1 network in OSCC. The results indicated that hsa_circ_0008309 may be a potential biomarker for OSCC. [ABSTRACT FROM AUTHOR]

Background. Circular RNAs (circRNAs) are a type of covalently closed loop structure of endogenous RNAs. Recent studies have shown that circular RNAs may play an important role in human cancer. However, there is limited information on the function of circRNA in oral squamous cell carcinoma (OSCC). Methods. Hsa_circ_001242 expression levels in 40 paired OSCC tissues and four OSCC cell lines were selected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_001242 in OSCC. Results. Hsa_circ_001242 was significantly downregulated in OSCC tissues compared to paired adjacent normal tissues (P<0.001). Hsa_circ_001242 expression levels were significantly downregulated in four OSCC cell lines (SCC-9, SCC-15, SCC25, and CAL-27) than in human normal oral keratinocyte (HOK) cell lines. Moreover, the expression level of hsa_circ_001242 was negatively correlated with tumor size and T stage (P<0.05). The area under the ROC curve was 0.784. Conclusion. This study showed that hsa_circ_001242 was significantly downregulated in OSCC and may act as a potential novel biomarker for the diagnosis and treatment of OSCC. [ABSTRACT FROM AUTHOR]

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12885-019-5593-5. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC), which originates from mucosal epithelium in the oral cavity, pharynx and larynx, is the sixth most common malignancy in the world. The prognosis of HNSCC is not satisfactory due to metastasis, resulting in 5-year survival rates ranging from 65.9 to 67.2%. Previously, we developed a method to evaluate the effect prodrug-activating suicide gene (PA-SG) therapy on the proliferation of HNSCC. The present study investigated PA-SG therapy on metastatic HNSCC by wound-healing assay and our previously established method. HSC-3 cells with stable expression of suicide genes thymidine kinase (TK) or cytosine deaminase (CD) were treated with prodrugs ganciclovir (GCV) or 5-fluorocytosine (5-FC), respectively. Both GCV and 5-FC inhibited HSC-3 proliferation while the bystander effect of CD/5-FC was greater compared with that of TK/GCV. GCV showed a greater anti-migration effect compared with that of 5-FC. To the best of our knowledge, the present study is the first to evaluate the anti-migratory and anti-proliferative effects of PA-SG therapies on metastatic HNSCC. This may also serve as a general method to quantify other types of PA-SC therapy. The present results demonstrated that PA-SG therapy is a promising treatment for anti-metastatic HNSCC therapy development. [ABSTRACT FROM AUTHOR]

Background: We previously described several abnormally expressed long non-coding RNA (lncRNA) in tong squamous cell carcinomas (TSCCs) that might be associated with tumor progression. In the present study, we aimed to investigate the role of abnormally expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) lncRNA in the metastatic potential of TSCC cells and its molecular mechanisms.Methods: Expression levels of MALAT-1 lncRNA were examined via quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in 127 TSCC samples as well as paired adjacent normal tissues and lymph node metastases (if exist). Lentiviral vectors expressing short hairpin RNA (shRNA) were used to knock down the expression of MALAT1 gene in two TSCC cell lines (CAL27 and SCC-25) with relatively higher MALAT-1 expression. Proliferational ability of the TSCC cells was analyzed using water soluble tetrazolium-1 (WST-1) assay. Metastatic abilities of TSCC cells were estimated in-vitro and in-vivo. We also performed a microarray-based screen to identify the genes influenced by MALAT-1 alteration, which were validated by real-time PCR analysis.Results: Expression of MALAT-1 lncRNA was enhanced in TSCCs, especially in those with lymph node metastasis (LNM). Knockdown (KD) of MALAT-1 lncRNA in TSCC cells led to impaired migration and proliferation ability in-vitro and fewer metastases in-vivo. DNA microarray analysis showed that several members of small proline rich proteins (SPRR) were up-regulated by KD of MALAT-1 lncRNA in TSCC cells. SPRR2A over-expression could impair distant metastasis of TSCC cells in-vivo.Conclusion: Enhanced expression of MALAT-1 is associated with the growth and metastatic potential of TSCCs. Knock down of MALAT-1 in TSCCs leads to the up-regulation of certain SPRR proteins, which influenced the distant metastasis of TSCC cells. [ABSTRACT FROM AUTHOR]

The occurrence and prognosis of head and neck squamous cell cancer (HNSC) is closely associated with human papillomavirus (HPV) infection. Transmembrane channel-like 8 (TMC8) is a key gene affecting the susceptibility of HPV and that plays an important role in T cell regulation. However, the mechanism by which TMC8 affects T cells and whether it further affects the prognosis of patients with HNSC remains unclear. In the present study, oral cancer cell lines and independent tumor specimens were used to detect TMC8 expression in HNSC. Differential expression of TMC8, methylation status, function and associated signaling pathways were further analyzed. Then, multiple databases were cross-analyzed for the relationship of TMC8 with immune cell infiltration and its impact on the prognosis of numerous types of cancer. The results showed that TMC8 was upregulated in HNSC and high expression was predictive of an improved prognosis. Furthermore, TMC8 was concentrated in multiple immune-associated signaling pathways and the expression of TMC8 was associated with the infiltration of CD4+ T cells and their subsets, including CD8+ T cells, B cells and macrophages, suggesting that TMC8 may play an anti-HPV role by regulating CD4+ T cells. Thus, TMC8 plays an anti-HPV role by regulating the infiltration level of CD4+ T cells, and could therefore be used as a potential prognostic marker for patients with HNSC. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a common oral and maxillofacial malignant tumor with high rates of metastasis and mortality. Circular RNAs (circRNAs), a type of non-coding RNA, are involved in the development of a variety of tumors. The roles of circRNAs in OSCC are unclear; in this study, the correlation between the circRNA hsa_circ_0055538, previously identified by high-throughput sequencing, and the biological behavior of OSCC was evaluated.Methods: circRNA expression was evaluated using patient tissue samples and various OSCC cell lines. The effects of overexpression and knockdown were evaluated by lentiviral infection and siRNA transfection of the SCC9 and CAL27 cell lines. Migration, invasion, apoptosis, and the expression of proteins in the p53 signaling pathway were evaluated. Infected cells were injected into nude mice to evaluate tumorigenesis.Results: Low hsa_circ_0055538 expression levels were verified in tumor tissues and OSCC cell lines. Clinical data analysis showed that the expression level is related to the degree of tumor differentiation. Lentiviral infection and siRNA transfection of SCC9 and CAL27 cell lines revealed that changes in circRNA expression significantly affected the malignant biological behavior of OSCC cells. Importantly, nude mouse experiments showed that high expression of hsa_circ_0055538 inhibited tumor growth. Finally, hsa_circ_0055538 may affect the development of OSCC via the p53/Bcl-2/caspase signaling pathway.Conclusions: Our results indicated that hsa_circ_0055538 is involved in OSCC via the p53 signaling pathway and may be a diagnostic and/or prognostic marker as well as a therapeutic target. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a common and rampant malignancy of the head and neck. However, its pathogenesis remains unclear. In this study, we have investigated the effects of circular RNA hsa_circ_009755 on proliferation, migration, invasion, and apoptosis in OSCC cells in vitro. Eight pairs of OSCC and normal adjacent tissues were selected to detect the differential expression of circRNAs by high-throughput sequencing. circRNA hsa_circ_009755 expression was determined by quantitative real-time polymerase chain reaction in OSCC tissues and cell lines. CCK-8, wound healing, Transwell, and flow cytometry assays were used to determine OSCC cell proliferation, migration, invasion, and apoptosis, respectively. The expression of hsa_circ_009755 was low in OSCC tissues and three OSCC cell lines. Silencing hsa_circ_009755 significantly enhanced the proliferation, migration, and invasion and suppressed the apoptosis of OSCC cells. Therefore, hsa_circ_009755 may be important in the tumorigenesis of OSCC. • Hsa_circ_009755 is downregulated in oral squamous cell carcinoma. • Silencing hsa_circ_009755 promotes growth and metastasis of oral squamous cell carcinoma. • Hsa_circ_009755 acts as a potential biomarker for OSCC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is an oral cavity malignancy which is the eighth most common cancer. However, the molecular mechanisms underlying the pathogenesis of OSCC remain largely unknown, and effective methods for the prognosis and diagnosis of this disease are lacking. Circular RNAs (circRNAs) are widely expressed among mammals. A growing number of studies have shown that circRNA expression is altered in cancers. In this study, we investigated the role of hsa_circ_0004491 in OSCC cell migration and invasion and examined the clinical characteristics associated with its expression. Hsa_circ_0004491 expression was examined in 40 paired OSCC and normal tissue samples using quantitative real-time PCR (qRT-PCR). Wound healing, transwell and western blotting assays were conducted in OSCC cells up- or down-regulation of hsa_circ_0004491 to evaluate changes in cell migration, invasion and protein expression. qRT-PCR analysis revealed that hsa_circ_0004491 was significantly downregulated in OSCC tissues compared with paired normal tissues (P < 0.001), and this low expression was associated with lymph node metastasis (P = 0.0398; area under ROC curve = 0.7510). Hsa_circ_000449 silencing or overexpression significantly affected the invasion and migration abilities of OSCC cells. Western blotting analysis showed that EMT-related proteins expression was significantly changed after hsa_circ_000449 silencing or overexpression. The expression level of hsa_circ_0004491 affects the migration and invasion of OSCC cells. Hsa_circ_0004491 may therefore play a role in the progression of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]