Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

BACKGROUND: The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). METHODS: A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. RESULTS: In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. CONCLUSIONS: The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

HHLA2 is more significantly associated with poor prognosis in TSCC than PD-L1.

BACKGROUND: The incidence and mortality of tongue squamous cell carcinoma have shown an alarming increase in recent years. This study aimed to investigate the potential of HHLA2 as an immune checkpoint in comparison to PD-L1. METHODS: We obtained RNA-seq data from TCGA to study HHLA2 and PD-L1 expression across various tissues. Using the CIBERSORT package, we estimated cell type abundances within mixed populations based on gene expression profiles. Immunohistochemistry was performed to analyze HHLA2 and PD-L1 expression in Tongue squamous cell carcinoma. Prognostic evaluation was carried out with Kaplan-Meier curves and the log-rank test. To explore factors affecting HHLA2, univariate and multivariate Cox regression analyses were conducted with the COX regression model. Additionally, we used single-cell RNA sequencing data from the GEO database for gene set enrichment analysis with genes strongly correlated with HHLA2. RESULTS: Our analysis of RNA-seq data unveiled a significant upregulation of HHLA2 and PD-L1 expression in primary tumors when compared with normal tissue. HHLA2 exhibited a positive expression rate of 36.9%, while PD-L1 had a positive expression rate of 24.6%. HHLA2 emerged as a noteworthy independent risk factor impacting the overall survival of Tongue squamous cell carcinoma patients. The analysis of scRNA-seq data shed light on the involvement of HHLA2 in key pathways related to cell cycle regulation and interferon alpha/beta signaling. CONCLUSIONS: This study suggests that in the context of Tongue squamous cell carcinoma, HHLA2 may represent a more promising target for immunotherapy when compared with PD-L1.

A novel nomogram for predicting overall survival in patients with tongue squamous cell carcinoma using clinical features and MRI radiomics data: a pilot study.

OBJECTIVE: Tongue squamous cell carcinoma (TSCC) accounts for 43.4% of oral cancers in China and has a poor prognosis. This study aimed to explore whether radiomics features extracted from preoperative magnetic resonance imaging (MRI) could predict overall survival (OS) in patients with TSCC. METHODS: The clinical imaging data of 232 patients with pathologically confirmed TSCC at Xiangyang No. 1 People's Hospital were retrospectively analyzed from February 2010 to October 2022. Based on 2-10 years of follow-up, patients were categorized into two groups: control (healthy survival, n = 148) and research (adverse events: recurrence or metastasis-related death, n = 84). A training and a test set were established using a 7:3 ratio and a time node. Radiomics features were extracted from axial T2-weighted imaging, contrast-enhanced T1-weighted imaging, and diffusion-weighted imaging (DWI) sequences. The corresponding radiomics scores were generated using the least absolute shrinkage and selection operator algorithm. Kaplan-Meier and multivariate Cox regression analyses were used to screen for independent factors affecting adverse events in patients with TSCC using clinical and pathological results. A novel nomogram was established to predict the probability of adverse events and OS in patients with TSCC. RESULTS: The incidence of adverse events within 2-10 years after surgery was 36.21%. Kaplan-Meier analysis revealed that hot pot consumption, betel nut chewing, platelet-lymphocyte ratio, drug use, neutrophil-lymphocyte ratio, Radscore, and other factors impacted TSCC survival. Multivariate Cox regression analysis revealed that the clinical stage (P < 0.001), hot pot consumption (P < 0.001), Radscore 1 (P = 0.01), and Radscore 2 (P < 0.001) were independent factors affecting TSCC-OS. The same result was validated by the XGBoost algorithm. The nomogram based on the aforementioned factors exhibited good discrimination (C-index 0.86/0.81) and calibration (P > 0.05) in the training and test sets, accurately predicting the risk of adverse events and survival. CONCLUSION: The nomogram constructed using clinical data and MRI radiomics parameters may accurately predict TSCC-OS noninvasively, thereby assisting clinicians in promptly modifying treatment strategies to improve patient prognosis.

Identification and validation of autophagy-related genes influenced by paris polyphylla in tongue cancer using network pharmacology.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) represents the most prevalent form of head and neck squamous cell carcinomas, comprising approximately one-third of all oral cancers. Paris polyphylla(PP) exhibit promising anti-tumor properties, yet their underlying mechanisms remain elusive. This study offers novel insights into the molecular mechanisms underlying TSCC treatment with PP and establishes a theoretical basis for their clinical application. METHODS: Employing transcriptomics and network pharmacology methodologies, we identified autophagy-related key genes associated with the effects of PP. These genes were subjected to KEGG and GO enrichment analyses to determine their related functions. In vitro, CAL-27 cells were treated with 10, 30, and 60 µg/ml of PP for 24 h to assess tumor cell proliferation, apoptosis, and autophagy-related markers. KEY FINDINGS: Molecular docking of MAPK3 and PSEN1 with PP revealed stable hydrogen bond interactions, indicating the therapeutic potential of these saponins in TSCC through the autophagy pathway. In vitro experiments demonstrated significant inhibition of proliferative activity in tongue squamous carcinoma CAL-27 cells and promotion of tumor cell apoptosis by PP. Western blot analysis confirmed alterations in the expression of autophagy markers P62, LC3B, and Beclin1 following treatment, suggesting activation of the autophagy pathway. CONCLUSIONS: Our results suggest that PP inhibits tumor cells through the autophagy pathway, in which MAPK3 and PSEN1 play a role as potential functional molecules.

Associations between adolescents watching pornography and poor mental health in three Swedish surveys.

The aim of this study was to examine the association between watching pornography and poor mental health in three repeated cross-sectional surveys in Sweden (2004, 2009, 2014) among high school seniors (13,277 students) with an average age of 18 years. The same index questions concerning ever having watched pornography and the frequency of watching pornography during the last year were combined with three different measures of psychological health and background control variables in multiple logistic regression and forward stepwise logistic regression models. The repeated cross-sectional surveys did not find any consistent associations across years between poor mental health and ever having watched pornography or the frequency of watching pornography. Having watched deviant pornography (containing violence, children and/or animals) was associated with poor mental health among boys in two surveys but only in one survey among girls. Other characteristics, such as mother's unemployment (especially boys), parenting style (especially high controlling parents among boys) and experiences of sexual abuse (especially penetrating abuse among girls), were more consistently and strongly associated to poor mental health across the three surveys. This study stresses the importance of controlling for multiple background variables when studying the association between watching pornography and mental health, since the association might primarily be explained by underlying confounding variables.

Circular RNA circCLK3 promotes the progression of tongue squamous cell carcinoma via miR-455-5p/PARVA axis.

A previous study has elucidated that circular RNA circCLK3 acts as an oncogenic gene in cervical cancer. However, the role and regulatory mechanism of circCLK3 in tongue squamous cell carcinoma (TSCC) remain unknown. Quantitative real-time PCR was used to examine targeted gene expression in different groups. Cell viability and proliferation were investigated by MTT and 5-ethynyl-2'-deoxyuridine assays. Cell migration and invasion were detected by Transwell assays, and cell apoptosis was measured by flow cytometry analysis. The interaction among genes was investigated using luciferase reporter assay, RNA pull-down assay, and RNA immunoprecipitation assay. In the present study, our findings revealed the upregulated expression of circCLK3 in TSCC tissues and cell lines. CircCLK3 knockdown suppressed cell proliferation, migration invasion, and induced cell cycle arrest at G0/G1 phase in TSCC. Moreover, circCLK3 acted as a molecular sponge for miR-455-5p. PARVA was the target gene of miR-455-5p. Furthermore, the negative correlation between expression of miR-455-5p and circCLK3 or PARVA in TSCC tissues was discovered. Rescue assays indicated that PARVA overexpression reversed the circCLK3 knockdown-mediated inhibitory effects on the progression of TSCC. In summary, circCLK3 exerts its carcinogenic effects on TSCC progression via absorbing miR-455-5p to upregulate PARVA, which expands our knowledge on the underlying mechanism of TSCC.

LINC00958 promotes the proliferation of TSCC via miR-211-5p/CENPK axis and activating the JAK/STAT3 signaling pathway.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most common oral tumors. Recently, long intergenic noncoding RNA 00958 (LINC00958) has been identified as an oncogene in human cancers. Nevertheless, the role of LINC00958 and its downstream mechanisms in TSCC is still unknown. METHODS: The effect of LINC00958 on TSCC cells proliferation and growth were assessed by CCK-8, colony formation, 5-Ethynyl-2'-deoxyuridline (EdU) assay and flow cytometry assays in vitro and tumor xenograft model in vivo. Bioinformatics analysis was used to predict the target of LINC00958 in TSCC, which was verified by RNA immunoprecipitation and luciferase reporter assays. RESULTS: LINC00958 was increased in TSCC tissues, and patients with high LINC00958 expression had a shorter overall survival. LINC00958 knockdown significantly decreased the growth rate of TSCC cells both in vitro and in vivo. In mechanism, LINC00958 acted as a ceRNA by competitively sponging miR-211-5p. In addition, we identified CENPK as a direct target gene of miR-211-5p, which was higher in TSCC tissues than that in adjacent normal tissues. Up-regulated miR-211-5p or down-regulated CENPK could abolish LINC00958-induced proliferation promotion in TSCC cells. Furthermore, The overexpression of CENPK promoted the expression of oncogenic cell cycle regulators and activated the JAK/STAT3 signaling. CONCLUSIONS: Our findings suggested that LINC00958 is a potential prognostic biomarker in TSCC.

Prediction of the degree of pathological differentiation in tongue squamous cell carcinoma based on radiomics analysis of magnetic resonance images.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is one of the most difficult malignancies to control. It displays particular and aggressive behaviour even at an early stage. The purpose of this paper is to explore the value of radiomics based on magnetic resonance fat-suppressed T2-weighted images in predicting the degree of pathological differentiation of TSCC. METHODS: Retrospective analysis of 127 patients with TSCC who were randomly divided into a primary cohort and a test cohort, including well-differentiated, moderately differentiated and poorly differentiated. The tumour regions were manually labelled in fat-suppressed T2-weighted imaging (FS-T2WI), and PyRadiomics was used to extract radiomics features. The radiomics features were then selected by the least absolute shrinkage and selection operator (LASSO) method. The model was established by the logistic regression classifier using a 5-fold cross-validation method, applied to all data and evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. RESULTS: In total, 1132 features were extracted, and seven features were selected for modelling. The AUC in the logistic regression model for well-differentiated TSCC was 0.90 with specificity and precision values of 0.92 and 0.78, respectively, and the sensitivity for poorly differentiated TSCC was 0.74. CONCLUSIONS: The MRI-based radiomics signature could discriminate between well-differentiated, moderately differentiated and poorly differentiated TSCC and might be used as a biomarker for preoperative grading.

MiR-26a/miR-26b represses tongue squamous cell carcinoma progression by targeting PAK1.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is the most common oral malignancy. Previous studies found that microRNA (miR)-26a and miR-26b were downregulated in TSCC tissues. The current study was designed to explore the effects of miR-26a/miR-26b on TSCC progression and the potential mechanism. METHODS: Expression of miR-26a, miR-26b and p21 Activated Kinase 1 (PAK1) in TSCC tissues and cell lines was detected by reverse transcription- quantitative polymerase chain reaction (RT-qPCR). Flow cytometry analysis was performed to examine cell cycle and apoptosis. Transwell assay was conducted to evaluate the migrated and invasive abilities of SCC4 and Cal27 cells. In addition, western blot assay was employed to analyze the protein level. Glucose assay kit and lactate assay kit were utilized to analyze glycolysis. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to explore the relationship between miR-26a/miR-26b and PAK1. Xenograft tumor model was constructed to explore the role of miR-26a/miR-26b in vivo. RESULTS: Both miR-26a and miR-26b were underexpressed, while PAK1 was highly enriched in TSCC. Overexpression of miR-26a and miR-26b inhibited TSCC cell cycle, migration invasion and glycolysis, while promoted cell apoptosis. Both miR-26a and miR-26b directly targeted and negatively regulated PAK1 expression. Introduction of PAK1 partially reversed miR-26a/miR-26b upregulation-mediated cellular behaviors in TSCC cells. Gain of miR-26a/miR-26b blocked TSCC tumor growth in vivo. CONCLUSION: MiR-26a/miR-26b repressed TSCC progression via targeting PAK1 in vitro and in vivo, which enriched our understanding about TSCC development and provided new insights into the its treatment.

TUG1/miR-133b/CXCR4 axis regulates cisplatin resistance in human tongue squamous cell carcinoma.

BACKGROUND: Long noncoding RNA taurine upregulated 1 (TUG1) has been reported to play an important role in human cancers. However, little is known about the role of TUG1 in drug resistance and its mechanism in tongue squamous cell carcinoma (TSCC). METHODS: Twenty-one cisplatin-sensitive or resistant TSCC patients were enrolled in this study. Cisplatin-resistant cells (SCC25/CDDP and CAL27/CDDP) were used for experiments in vitro. Transfection was performed using Lipofectamine 2000 transfection reagent. The levels of TUG1, microRNA-133b (miR-133b) and cysteine-X-cysteine chemokine receptor 4 (CXCR4) were measured by quantitative real-time polymerase chain reaction or western blot. The cisplatin resistance was investigated by cell viability, transwell invasion and apoptosis assays. The interactions among TUG1, miR-133b and CXCR4 were evaluated by luciferase reporter assay and RNA immunoprecipitation. Murine xenograft model was established using the stably transfected CAL27/CDDP cells. RESULTS: TUG1 expression was elevated in cisplatin-resistant TSCC tissues and cells compared with that in sensitive group and its knockdown inhibited cisplatin resistance to SCC25/CDDP and CAL27/CDDP cells. miR-133b was targeted via TUG1 and its overexpression suppressed cisplatin resistance. Moreover, CXCR4 was a target of miR-133b. CXCR4 silence repressed cisplatin resistance, which was reversed by miR-133b knockdown. The level of CXCR4 protein was decreased by inhibition of TUG1 and recuperated by miR-133b knockdown. Besides, interference of TUG1 attenuated tumor growth by regulating miR-133b and CXCR4 in vivo. CONCLUSION: Downregulation of TUG1 impeded cisplatin resistance in TSCC-resistant cells by mediating miR-133b and CXCR4, indicating TUG1 as a promising target for TSCC chemotherapy.

NIT2 overexpression predicts poor prognosis in tongue squamous cell carcinoma patients.

There is disputable on the role of nitrilase-like 2 (NIT2) in cancer. Its expression and its relationship with clinicopathological features in tongue squamous cell carcinoma (TSCC) are not yet clear. The purpose of this study is to investigate the expression of NIT2 in TSCC and its correlation with clinicopathological characteristics in TSCC patients. Through proteomic identification, we found that the protein NIT2 was related to the development of TSCC. q-PCR, western blot and immunohistochemistry techniques were applied to detect the expression of NIT2 in TSCC. The relationship between the expression of NIT2 and clinicopathological features was analyzed by Chi square tests. The results showed the expression of NIT2 in TSCC was significantly higher than that in normal tongue tissues (p < 0.05). Univariate and multivariate analysis showed that the positive expression of NIT2 and N classification were associated with decreased disease-free survival rate (DFS) and overall survival (OS) (p < 0.05). The results suggested that NIT2 is overexpressed in TSCC and NIT2 may be a potential therapeutic target for TSCC.

CRNDE promotes cell tongue squamous cell carcinoma cell growth and invasion through suppressing miR-384.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is an aggressive head and neck malignancy. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play important roles in diverse biological cell processes, such as cell development, fate decisions, cell differentiation, cell migration, and invasion. In our study, we showed that long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) expression was upregulated in TSCC cell lines and tissues. Overexpression of CRNDE increased the TSCC cell proliferation, cell cycle, and cell invasion. Moreover, ectopic expression of CRNDE inhibited the miR-384 expression in the SCC1 cell and increased the Kirsten Ras (KRAS), cell division cycle 42, and insulin receptor substrate 1 expression, which were the direct target genes of miR-384. We demonstrated that the miR-384 expression was downregulated in the TSCC samples compared with the paired adjacent nontumor samples. The expression of CRNDE was negatively correlated with the expression of miR-384 in the TSCC samples. Overexpression of miR-384 suppressed TSCC cell proliferation, cell cycle, and invasion. Furthermore, we demonstrated that CRNDE promoted TSCC cell proliferation and invasion through inhibiting miR-384 expression. These results suggested that CRNDE acts as an oncogene in the development of TSCC, which partially occurs through inhibiting miR-384 expression.

Numb inhibits epithelial-mesenchymal transition via RBP-Jκ-dependent Notch1/PTEN/FAK signaling pathway in tongue cancer.

BACKGROUND: Oral cancer has been estimated as the sixth most frequent solid cancer all over the world, in which tongue squamous cell carcinoma (TSCC) is the most common type of oral cancers. However, the mechanism of TSCC metastasizing to lymph node and distant sites has not been completely understood. METHODS: In this study, RT-qPCR method was used to detect the mRNA level of Numb, PTEN and Notch1 genes, as well as EMT-associated genes. Western blot assay was utilized to detect protein level of these genes. In addition, we determined cell proliferation by MTT assay and employed transwell invasion assay and wound healing assay to probe the abilities of invasion and migration, respectively. To investigate the role of PTEN, its inhibitor VO-Ohpic trihydrate was used to treat SCC-4 and CAL27 cells. RESULTS: We found that Numb expression was downregulated in SCC-9 and CAL-27 cells compared to NHOK cells. Instead, Notch1 level in SCC-9 and CAL-27 cells were higher than that in NHOK cells. Furthermore, the results showed that Numb overexpression significantly suppressed proliferation, migration and invasion of SCC-9 and CAL-27 cells via regulating Notch1 signaling and EMT-related genes expression. By contrast, we observed that RBP-Jκ knockdown had an inhibitory role in proliferation, migration and invasion of SCC-9 and CAL-27 cells. In cells with Numb overexpression or RBP-Jκ knockdown, p-FAK and EMT-related genes were remarkably regulated. CONCLUSIONS: Our findings provide new mechanism of understanding the metastasis of TSCC and help develop therapeutic strategies for treating tongue cancer.

Long noncoding RNA GIHCG enhanced tongue squamous cell carcinoma progression through regulating miR-429.

Long noncoding RNAs play essential roles in cancer development and progression. Here, we tried to investigate the role of GIHCG in the progression and metastasis of tongue squamous cell carcinoma (TSCC). In our study, we showed that that the expression level of GIHCG was upregulated in TSCC tissues and cell lines. In addition, we indicated that high GIHCG expression was positively associated with poor overall survival. Moreover, ectopic expression of GIHCG enhanced TSCC cell cycle, proliferation, and migration. Elevated expression of GIHCG inhibited the miR-429 expression in TSCC cells. We demonstrated that the expression level of miR-429 was lower in TSCC tissues and cell lines. Low miR-429 expression was positively associated with poor overall survival. We then determined the correlation between miR-429 and GIHCG expression levels. A statistically significantly inverse correlation was observed between miR-429 and GIHCG expression levels in TSCC tissues. In addition, overexpression of miR-429 suppressed the TSCC cell cycle, proliferation, and migration. Elevated expression of GIHCG promoted TSCC cell cycle, proliferation, and migration through regulating miR-429 expression. These results suggested that GIHCG increased TSCC progression through negative modulation of miR-429. Our results suggested that GIHCG/miR-429 might play a vital role in TSCC progression.

Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/ß-catenin signaling pathway.

BACKGROUND: Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. METHODS: The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues. The correlation between AFAP1-AS1 and the clinicopathological features was evaluated using the chi-square test. The effects of AFAP1-AS1 on TSCC cells were determined via a CCK-8 assay, clone formation assay, flow cytometry, wound healing assay and transwell assay. Furthermore, the effect of AFAP1-AS1 knockdown on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, CAL-27 cells with AFAP1-AS1 knockdown were subcutaneously injected into nude mice to evaluate the effect of AFAP1-AS1 on tumor growth in vivo. RESULTS: In this study, we found that lncRNA AFAP1-AS1 was increased in TSCC tissues and that patients with high AFAP1-AS1 expression had a shorter overall survival. Short hairpin RNA (shRNA)-mediated AFAP1-AS1 knockdown significantly decreased the proliferation of TSCC cells. Furthermore, AFAP1-AS1 silencing partly inhibited cell migration and invasion. Inhibition of AFAP1-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of EMT-related genes (SLUG, SNAIL1, VIM, CADN, ZEB1, ZEB2, SMAD2 and TWIST1) in TSCC cells. In addition, CAL-27 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on tumorigenesis in vivo. Downregulation of AFAP1-AS1 suppressed tumor growth and inhibited the expression of EMT-related genes (SLUG, SNIAL1, VIM, ZEB1, NANOG, SMAD2, NESTIN and SOX2) in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA AFAP1-AS1 to suppress TSCC progression, and these results elucidate a novel potential therapeutic strategy for TSCC.

Reliability and Validity of the Trauma Symptom Checklist for Children and Trauma Symptom Checklist for Young Children Screeners in a Clinical Sample.

This study reports on the reliability and validity for two measures developed for screening of symptoms in child sexual abuse (CSA)-the Trauma Symptom Checklist for Children-Screening Form (TSCC-SF) and the Trauma Symptom Checklist for Young Children-Screening Form (TSCYC-SF). The sample of 200 children and caregivers received outpatient treatment. Internal consistencies ranged from an alpha of 0.79-0.85. Concurrent validity was demonstrated by correlations with the TSCC and TSCYC. The TSCC-SF General Trauma (GT) was only correlated Child Behavior Checklist (r = .236 for the Anxious Depressed Scale with the TSCC GT; however, all Child Behavior Checklist scales correlated with the TSCYC GT ranging from .422 to .692, and with the SC with r = .713), and the Children's Attributional and Perceptual Scale. Findings support reliability and validity reported elsewhere. The TSCC-SF and TSCYC-SF show promise for screening and triage of CSA victims in many settings.

PDGF-D/PDGFRß promotes tongue squamous carcinoma cell (TSCC) progression via activating p38/AKT/ERK/EMT signal pathway.

Platelet-derived growth factor D (PDGF-D) signaling plays significant roles during the development and progression of human malignancies via interacting with the receptor of PDGF-D (PDGFR). Meanwhile, the majority of human tumor metastasis is closely associated with epithelial-mesenchymal transition (EMT). However, the underlying mechanism between PDGF-D/PDGFR signaling and EMT which involved in tumor metastasis remain dismal. This study aimed to investigate the role of PDGF-D signaling during EMT process of tongue squamous cell carcinoma (TSCC). In our study, the expression of PDGF-D and PDGFR were examined in primary TSCC samples and the expression of PDGF-D was also determined in TSCC cell lines. In addition, the correlation between PDGF-D expression and TSCC aggressive histopathological features was analyzed. Our results implied that upregulation of PDGFRß in UM1 cells induced with exogenous PDGF-D can remarkably promote tumor cells invasiveness; conversely, when using small interfering RNA (siRNA), the invasiveness can be severely prohibited. Furthermore, PDGF-D downstream signal molecules p38, AKT, ERK and EMT biomarkers (E-cadherin, N-cadherin, Vimentin and snail) were measured using Western blot. Our results showed that PDGF-D can induce p38, AKT and ERK phosphorylation; downregulate epithelial markers and upregulate mesenchymal markers. On the contrary, PDGFRß siRNA significantly prohibited p38, AKT and ERK phosphorylation; inhibited EMT process. Function analysis revealed that PDGFRß siRNA obviously interfered with UM1 cell migration and invasion, according to transwell and wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the PDGF-D/PDGFRß axis in TSCC, and then involved in the tumor cell invasion via activation of p38/AKT/ERK/EMT pathway.

Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes.

BACKGROUND: Clinical indexes are often selected as relevant factors for constructing prognostic models of tongue squamous cell carcinoma (TSCC) patients, while factors related to therapeutic targets are less frequently included. As Apigenin (API) shows anti-tumor properties in many tumors, in this study, we construct a novel prognostic model for TSCC patients based on Apigenin-associated genes through transcriptomic analysis. METHODS: The effect of Apigenin (API) on the cell characteristics of TSCC cells was measured by several phenotype experiments. RNA-seq was executed to ensure differentially expressed genes (DEGs) in squamous cell carcinoma-9 (SCC-9) cells after API treatment. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to verify the expression of API-related genes. Then, combined with the gene expression data and relevant individual information of TSCC samples acquired from The Cancer Genome Atlas (TCGA), an API-related model was built through Lasso regression and multivariate Cox regression. A receiver operating characteristic (ROC) curve and a nomogram and calibration curve were created to forecast patient outcomes to improve the clinical suitability of the API-related signature. The relationships between the two risk groups and function enrichment, immune infiltration characteristics, and drug susceptibility were analyzed. RESULTS: We demonstrated that API could inhibit the malignant behavior of TSCC cells. Among API-related genes, TSCC cells treated with API, compared to the control group, have higher levels of transmembrane protein 213 (TMEM213) and G protein-coupled receptor 158 (GPR158), and lower levels of caspase 14 (CASP14) and integrin subunit alpha 5 (ITGA5). An 7 API-associated gene model was built through Lasso regression and multivariate Cox regression that could direct TSCC prognostic status and tumor immune cell infiltration. In addition, we acquired 6 potential therapeutic agents for TSCC based on the prognostic model. CONCLUSIONS: Our research suggested the inhibition effect of API on TSCC cells and provided a novel prognostic model combined with therapeutic factors that can guide the prognosis of TSCC and clinical decision-making in TSCC.

Tongue Squamous Cell Carcinoma Prognosis Can Be Effectively Predicted by LncRNA LIPH4: A Prospective Study.

Purpose: LIPH4 has been identified as an oncogenic lncRNA in different malignant diseases. This research aims to elucidate the link between the expression of LIPH4 and its prognostic application in tongue squamous cell carcinoma (TSCC). Methods: To assess the expression of LIPH4, 142 TSCC and normal cases, respectively, which met the selection parameters, were used for qRT-PCR analysis. Furthermore, the association of LIPH4 expression with TSCC's clinicopathological features was identified via the Chi-square test. Moreover, the Kaplan-Meier test was used for calculating the survival rates, whereas the association of patient survival with prognostic factors was assessed with the help of Cox proportional hazard analysis. Results: The data indicated upregulated LIPH4 levels in TSCC samples than healthy samples. Furthermore, LIPH4 expression was associated with TSCC differentiation and stage, where increased expression indicated reduced disease-free survival (DFS) and overall survival (OS) rates. Additionally, advanced TSCC individuals with enhanced LIPH4 expression had reduced OS and DFS rates than those with reduced LIPH4 expression. Serum LIPH4 could be a promising diagnostic bio-index for TSCC, with an area under the curve of 0.8920 (95% CI = 0.8540-0.9299). These data revealed that the overexpression of LIPH4 might be a substantial prognostic factor for independently predicting the OS and DFS rates of TSCC patients. Conclusion: Altogether, this research revealed that the expression of LIPH4 expression is closely associated with TSCC progression and, therefore, can be employed as a biomarker for its prognosis.