Invasive Squamous Cell Carcinoma Research Articles

Histone Lysine Lactylation (Kla)-induced BCAM Promotes OSCC Progression and Cis-Platinum Resistance.

Histone lysine lactylation (Kla) plays a vital role in cancer progression. However, the prognostic value of histone Kla in oral squamous cell carcinoma (OSCC) remains unclear. OSCC RNA expression data were obtained from the TCGA and GEO databases. We explored the prognostic value of histone Kla in OSCC via constructing a Cox model and determined the role of Kla in OSCC drug susceptibility and tumor microenvironment (TME). In addition, the biological roles of candidate biomarkers were identified. A total of 1223 Kla-specific genes were obtained, with 228 DEKlaGs in OSCC. GO and KEGG enrichment analyses suggested that DEKlaGs contributed to inflammatory and cancer progression. A Cox model in accordance with BCAM, CGNL1, DGKG, and OLR1 could predict OSCC patient prognosis accurately. Subsequently, Kla-induced prognostic genes were identified to play a crucial role in OSCC drug therapy and TME. Moreover, BCAM was identified as a biomarker that promoted OSCC invasion, angiogenesis, and chemotherapy resistance. Kla was identified to be associated with OSCC prognosis, drug therapy, and TME. Histone Kla-induced BCAM was identified to play a crucial role during OSCC progression, suggesting that Kla is promising to be a novel therapeutic target for OSCC.

Validation of lymphovascular invasion as a predictor of lymph-node invasion in squamous cell carcinoma of the penis.

The aim of this study was to validate lymphovascular invasion (LVI) as a predictor of lymph-node invasion (LNI) in squamous cell carcinoma of the penis (SCCP). Within the Surveillance, Epidemiology, and End Results database (2010-2020), we identified SCCP patients who underwent lymphadenectomy with known LVI status. Univariable logistic regression models (LRMs) addressed LNI. Harrell's concordance index (c-index) quantified accuracy after 2000 bootstrap resamples for internal validation. Multivariable LRMs included the most informative, statistically significant predictors. Subgroup analyses were repeated in organ-confined (T1b-T2) and non-organ confined (T3-T4) stages. Of 586 SCCP patients, 219 (37%) had LVI. LVI was associated with higher rate of LNI (66 vs. 43%; P<0.001). Positive predictive value of LVI was 66 vs. 57% for negative predictive value. In multivariable LRMs, LVI independently predicted LNI (Odds ratio [OR]: 2.41; P<0.001). Bootstrap-adjusted c-index of multivariable model was 0.570 without LVI vs. 0.639 with LVI. In subgroup analyses, LVI independently predicted LNI in organ-confined (OR: 2.23; P<0.001) and in non-organ confined stages (OR: 3.10; P<0.001). In subgroup analyses, addition of LVI increased c-index from 0.530 to 0.595 in organ-confined and from 0.599 to 0.682 in non-organ confined. The current study validates LVI as an independent predictor of LNI in SCCP. LVI increases the accuracy of LNI predictions in the overall cohort as well as in organ-confined and non-organ confined stages. However, stage and grade even with the added consideration of LVI are not accurate enough to provide LNI prediction in individual patients.

Molecular and tumor microenvironmental characterization of HPV-negative invasive squamous cell carcinoma of the vulva

Molecular and tumor microenvironmental characterization of HPV-negative invasive squamous cell carcinoma of the vulva

CHRDL1 inhibits OSCC metastasis via MAPK signaling-mediated inhibition of MED29

BackgroundCHRDL1 belongs to a novel class of mRNA molecules. Nonetheless, the specific biological functions and underlying mechanisms of CHRDL1 in oral squamous cell carcinoma (OSCC) remain largely unexplored.MethodsRT-qPCR and immunohistochemical staining were employed to assess the mRNA and protein expression levels of the MED29 gene in clinical samples of OSCC. Additionally, RT-qPCR and Western Blot analyses were conducted to investigate the mRNA and protein expression levels of the MED29 gene specifically in OSCC. The impact of MED29 on epithelial-mesenchymal transition (EMT), invasion, and migration of OSCC was evaluated through scratch assay, transwell assay, and immunofluorescence staining. Furthermore, wound healing assay and Transwell assay were utilized to examine whether CHRDL1 influences the malignant behavior of OSCC by modulating MED29 in vitro. The regulatory role of CHRDL1 on MED29 was further elucidated in vivo through a tail vein lung metastasis model in nude mice.ResultsMED29 expression was elevated in tumor tissues of OSCC patients compared with adjacent cancer tissues. Moreover, in CAL27 and SCC25 cell lines, MED29 was upregulated and associated with increased cell migration and invasion abilities. Overexpression of MED29 facilitated EMT in OSCC cell lines, whereas knockdown of MED29 impeded EMT, resulting in diminished cell migration and invasion capacities. CHRDL1 exerted inhibitory effects on the expression of MED29, thereby suppressing EMT progression and consequently restraining the invasion and migration of OSCC cells. Furthermore, CHRDL1 mediated the inhibition of migration of OSCC cell lines to the OSCC through its regulation of MED29.ConclusionsMED29 facilitated the epithelial-mesenchymal transition process in OSCC, thereby promoting migration and invasion. On the other hand, CHRDL1 exerted inhibitory effects on the invasion and metastasis of OSCC by suppressing MED29 through the inhibition of the MAPK signaling pathway.

Comparative Study of Cutaneous Squamous Cell Carcinogenesis in Different Hairless Murine Models

Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis.

Diagnostic Accuracy of Computed Tomography and Clinical Examination in the Assessment of Mandibular Invasion of Oral Squamous Cell Carcinomas

Introduction: Computed tomography (CT) scan precisely shows soft and hard tissues in the same test hereby determines the lesion extension, involvement of regional node as well as of bone. Current study was aimed to evaluate the efficacy of clinical examination and CT to assess mandibular invasion in oral squamous cell carcinoma. Materials and methods: This cross-sectional study was conducted at Dhaka Dental College Hospital from July, 2016 to July, 2017 among conveniently selected 35 patients of histologically confirmed squamous cell carcinoma which was close to the mandible. The patients underwent proper clinical examination. CT scan was performed; preoperative staging and treatment plan was formulated according to the status of bone invasion. After mandibulectomy, the resected specimens were sent for histopathology. The findings from clinical examination and CT were then correlated with the gold standard, postoperative histopathology. Results: Clinical examination accurately detected 22 cases to have bone invasion and 8 cases with no bone invasion. It also gave 2 false positive and 3 false negative results. On the other hand CT accurately detected 24 cases to have bone invasion and 9 cases with no bone invasion. It provided one false positive and one false negative result. However, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of clinical examination were 88%, 80%, 91.67%, 72.73%, 85.71% respectively (p = 0.0002) and of CT were 96%, 90%, 96%, 90%, 94.28% respectively (p &lt; 0.0001). Clinical examination and CT were found sensitive enough and have an acceptable range of specificity as primary investigative modalities. CT scan outperforms clinical examination in terms of sensitivity, specificity, NPV, and accuracy. Conclusion: CT scan imaging is the method of choice for planning treatment in advanced oral squamous cell carcinoma. This study reveals how a CT scan can provide additional diagnostic value to detect bone invasion. Update Dent. Coll. j: 2024; 14(2): 21-26

Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.

Prediction of lymphovascular invasion in esophageal squamous cell carcinoma by computed tomography-based radiomics analysis: 2D or 3D ?

BackgroundTo compare the performance between one-slice two-dimensional (2D) and whole-volume three-dimensional (3D) computed tomography (CT)-based radiomics models in the prediction of lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC).MethodsTwo hundred twenty-four patients with ESCC (158 LVI-absent and 66 LVI-present) were enrolled in this retrospective study. The enrolled patients were randomly split into the training and testing sets with a 7:3 ratio. The 2D and 3D radiomics features were derived from the primary tumors’ 2D and 3D regions of interest (ROIs) using 1.0 mm thickness contrast-enhanced CT (CECT) images. The 2D and 3D radiomics features were screened using inter-/intra-class correlation coefficient (ICC) analysis, Wilcoxon rank-sum test, Spearman correlation test, and the least absolute shrinkage and selection operator, and the radiomics models were built by multivariate logistic stepwise regression. The performance of 2D and 3D radiomics models was assessed by the area under the receiver operating characteristic (ROC) curve. The actual clinical utility of the 2D and 3D radiomics models was evaluated by decision curve analysis (DCA).ResultsThere were 753 radiomics features from 2D ROIs and 1130 radiomics features from 3D ROIs, and finally, 7 features were retained to construct 2D and 3D radiomics models, respectively. ROC analysis revealed that in both the training and testing sets, the 3D radiomics model exhibited higher AUC values than the 2D radiomics model (0.930 versus 0.852 and 0.897 versus 0.851, respectively). The 3D radiomics model showed higher accuracy than the 2D radiomics model in the training and testing sets (0.899 versus 0.728 and 0.788 versus 0.758, respectively). In addition, the 3D radiomics model has higher specificity and positive predictive value, while the 2D radiomics model has higher sensitivity and negative predictive value. The DCA indicated that the 3D radiomics model provided higher actual clinical utility regarding overall net benefit than the 2D radiomics model.ConclusionsBoth 2D and 3D radiomics features can be employed as potential biomarkers to predict the LVI in ESCC. The performance of the 3D radiomics model is better than that of the 2D radiomics model for the prediction of the LVI in ESCC.

Energy Metabolic Profile in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Preliminary Landscape of Warburg Effect in Oral Cancer.

We hypothesized that cell energy metabolic profiles correlate with normal, dysplastic, and tumor cell/tissue statuses and may be indicators of aggressiveness in oral squamous cell carcinoma (OSCC) cells. The energy-related proteins that were differentially expressed in human OSCC fragments (n = 3) and their adjacent epithelial tissue (TAE) were verified using mass spectrometry (MS). Immunohistochemistry for 4-hydroxynonenal (4-HNE) was performed to evaluate the oxidative stress patterns in OSCC (n = 10), epithelial dysplasia (n = 9), and normal epithelial (n = 4) biopsies. The metabolic energy profile of OSCC aggressiveness was investigated in human OSCC cell lines with different levels of epithelial-mesenchymal transition proteins. The genes associated with the proteins found by MS in this study were analyzed using survival analysis (OS), whereas the genes associated with a poorer prognosis were analyzed using context-specific expression, Gene Ontology (GO) and Cancer Hallmarks for function enrichment analysis. The rationale for all experimental approach was to investigate whether the variation in energy metabolism profile accompanies the different phenotypes (from epithelial to mesenchymal) during the epithelial-mesenchymal transition. All OSCC fragments exhibited an increase in glycolysis-related proteins and a decrease in mitochondrial activity compared to the TAE region (p < 0.05), probably due to the downregulation of pyruvate dehydrogenase and antioxidant proteins. Additionally, the OSCC cell lines with a mesenchymal profile (SCC4, SCC9, and SCC25) had a lower mitochondrial mass and membrane potential and generated lower levels of reactive oxygen and nitrogen species than the TAE region. When we analyzed 4-HNE, the reactive species levels were increased in the epithelial regions of OSCC and potentially malignant lesions. A decrease in the levels of 4-HNE/reactive species was observed in the connective tissue underlying the dysplastic regions and the OSCC invasion zone. Based on this scenario, aggressive OSCC is associated with high glycolytic and oxidative metabolism and low mitochondrial and antioxidant activities, which vary according to the differentiation level of the tumor cells and the stage of carcinogenesis.

KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma.

In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC). The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR. A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC. This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung.

Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan-Meier survival analysis and Cox regression models were used to identify significant prognostic factors. The Kaplan-Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Single cell analysis revealed SFRP2 cancer associated fibroblasts drive tumorigenesis in head and neck squamous cell carcinoma

Understanding the mechanisms of invasion and metastasis in head and neck squamous cell carcinoma (HNSCC) is crucial for effective treatment, particularly in metastatic cases. In this study, we analyzed multicenter bulk sequencing and comprehensive single-cell data from 702,446 cells, leading to the identification of a novel subtype of cancer-associated fibroblasts (CAFs), termed Secreted Frizzled-Related Protein2 CAFs (SFRP2_CAFs). These cells, originating from smooth muscle cells, display unique characteristics resembling both myofibroblastic CAFs and inflammatory CAFs, and are linked to poorer survival outcomes in HNSCC patients. Our findings reveal significant interactions between SFRP2_CAFs and SPP1 tumor-associated macrophages, which facilitate tumor invasion and metastasis. Moreover, our research identifies Nuclear factor I/X (NFIX) as a key transcription factor regulating SFRP2_CAFs behavior, confirmed through gene regulatory network analysis and simulation perturbation.

The seven-day cumulative post-esophagectomy inflammatory response predicts cancer recurrence

BackgroundThe relationship between postoperative cumulative systemic inflammation and cancer survival needs to be investigated. We developed an approach to the prognostication of postoperative esophageal cancer by establishing low and high cut-off values for the C-reactive protein (CRP) area under the curve (AUC) at 7 and 14 days after esophagectomy.MethodsOne hundred and twenty-five consecutive patients with biopsy-proven invasive esophageal squamous cell carcinoma (SCC) who underwent esophagectomies were evaluated. Postoperative CRP levels were analyzed for the first 14 days after surgery. The AUC on days 7 and 14 were calculated and compared with clinicopathological features and survival. The cut-off values for CRP at 7 days (CRP 7 d) and 14 days (CRP 14 d) were 599 mg/L and 1153 mg/L, respectively.ResultsThe patients in the low CRP 7 d group had significantly better recurrence-free survival (RFS) and overall survival (OS), not that in the low CRP 14d group. The OS rates in the high CRP groups at PODs 1, 3, 10, and 14 were significantly lower than those in the low CRP groups. Postoperative complications were more common in the high CRP groups on PODs 3, 10, and 14. Univariate analyses revealed that pTNM stage, depth of tumor invasion, tumor location, lymph node involvement, and CRP 7 d were significant prognostic factors for both OS and RFS. The Cox proportional hazards model identified pTNM, tumor location, and CRP 7d as independent prognostic factors for the RFS and OS.ConclusionsEarly prediction of patients with postoperative complications, and adequate management will suppress the elevation of CRP 7 d and further suppress the CRP value in the late postoperative period, which may improve the prognosis of esophageal cancer patients after esophagectomy.

Prediction of preoperative lymph-vascular space invasion and survival outcomes of cervical squamous cell carcinoma by utilizing 18 F-FDG PET/CT imaging at early stage.

To establish nomograms for predicting preoperative lymph-vascular space invasion (LVSI) and survival outcomes of cervical squamous cell carcinoma (CSCC) based on PET/CT radiomics. One hundred and twenty-three patients with CSCC and LVSI status were enrolled retrospectively. Independent predictors of LVSI were identified through clinicopathological factors and PET/CT metabolic parameters. We extracted 1316 features from PET and CT volume of interest, respectively. Additionally, four models (PET-RS: radiomic signature of PET only; CT-RS: radiomic signature of CT only; PET/CT-RS + clinical data; PET/CT-RS: radiomic signature of PET and CT) were established to predict LVSI status. Calculation of radiomics scores of PET/CT was executed for assessment of the survival outcomes, followed by development of nomograms with radiomics (NR) or without radiomics (NWR). One hundred and twenty-three patients with pathologically confirmed CSCC had been categorized into two sets (training and testing sets). It was found that only maximum standardized uptake value (SUV max ) and squamous cell carcinoma antigen were independent predictors of LVSI. Meanwhile, the PET/CT-RS + clinical data outperformed the other three models in the training set [area under the curve (AUC): 0.91 vs. 0.861 vs. 0.81 vs. 0.814] and the testing set (AUC: 0.885 vs. 0.857 vs. 0.783 vs. 0.798). Additionally, SUV max and LVSI had been demonstrated to be independent prognostic indicators for progression-free survival and overall survival. Decision curve analysis and calibration curve indicated that NRs were superior to NWRs. The survival outcomes were assessed. PET/CT-based radiomic signature nomogram enables a new method for preoperative prediction of LVSI and survival prognosis for patients with CSCC.

Excision combined with ocular surface reconstruction followed by topical chemotherapy for ocular surface squamous neoplasia.

To investigate the visual prognosis of ocular surface squamous neoplasia (OSSN) after tumor resection and ocular surface reconstruction, and clarify factors that influence recurrence. Retrospective cohort study. Medical records of all patients who underwent surgical treatment for OSSN at our hospital between January 1996 and December 2019 were reviewed. Tumor size/location, histological classification, surgical procedure, intraoperative mitomycin-C use, and postoperative topical 5-fluorouracil (5-FU) administration were examined, and pre and postoperative visual acuity (VA) were compared to elucidate factors that influence disease recurrence. Tumor excision was performed in 70 eyes of 70 cases (43 men, 27 women; average age: 71.6 ± 12.6 years) with dysplasia (8 eyes), carcinoma in situ (26 eyes), and invasive squamous cell carcinoma (36 eyes). Tumors were found in the limbus (N = 59 eyes), palpebral conjunctiva (N = 8 eyes), and from the bulbar to palpebral conjunctiva (N = 3 eyes). Surgical procedures performed were limbal transplantation/keratoepithelioplasty (N = 29 eyes), cultivated oral mucosal epithelial transplantation (N = 3 eyes), and auto-conjunctival epithelium transplantation (N = 2 eyes). Ocular surface was reconstructed using amniotic membrane, donor cornea, or cultivated epithelial sheet. The mean follow-up was 38.6 ± 38.6 months (range, 2 months to 13.8 years). VA postoperatively improved in 25 (61.0%) cases. Recurrence occurred in 19 (27.1%) cases at from 2 to 50 months (median: 12.5 months) postoperative. Uni- and multivariate analyses revealed that presurgical tumor size and postoperative administration of 5-FU were significantly related to recurrence. Combined surgical excision and postoperative topical 5-FU administration effectively prevented OSSN recurrence, and ocular surface reconstruction contributed to improvement of VA.

The LINC00319 binding to STAT3 promotes the cell proliferation, migration, invasion and EMT process in oral squamous cell carcinoma

BackgroundLong non-coding RNA LINC00319 has been implicated in the progression of various cancers, including oral squamous cell carcinoma (OSCC). While our previous work has revealed some aspects of LINC00319's role in OSCC, including its upregulation and involvement in a competing endogenous RNA (ceRNA) mechanism, the full extent of its functions and regulatory mechanisms in OSCC progression remain to be fully elucidated. ObjectiveThis study aimed to investigate the function of LINC00319 in OSCC and its potential interaction with the STAT3 signaling pathway, thus uncovering novel regulatory mechanisms and therapeutic targets. MethodsBioinformatics analysis was performed using TCGA data to evaluate LINC00319 expression in OSCC tissues and its correlation with STAT3 signaling. The direct binding between LINC00319 and STAT3 was examined by RNA pull-down, FISH, and RIP assays. Functional experiments, including CCK-8, transwell migration and invasion assays, and western blot analysis of EMT markers and STAT3 pathway activation, were conducted to assess the effects of LINC00319 on OSCC cell behaviors and its interaction with the STAT3 signaling pathway. In vivo xenograft models were established to validate the role of LINC00319 in tumor growth and STAT3 activation. ResultsLINC00319 expression was significantly upregulated in OSCC tissues compared to normal tissues, and high LINC00319 expression correlated with STAT3 signaling activation. Mechanistically, LINC00319 directly bound to STAT3 protein and promoted its phosphorylation at Tyr705. LINC00319 overexpression enhanced, while its knockdown suppressed, the proliferation, migration, invasion, and EMT of OSCC cells. These oncogenic effects were mediated through STAT3 activation and could be reversed by the STAT3 inhibitor stattic. In vivo experiments further confirmed that LINC00319 silencing inhibited tumor growth and STAT3 phosphorylation. ConclusionThis study uncovers that LINC00319 promotes OSCC tumorigenesis by directly binding to and activating STAT3 signaling. These findings provide new insights into the regulatory mechanisms of STAT3 by long non-coding RNAs and highlight the potential of LINC00319 as a biomarker and therapeutic target in OSCC.

USP18 promotes the proliferation, invasion, and migration of head and neck squamous cell carcinoma by deubiquitinating PLK1

The ubiquitin specific peptidase 18 (USP18), a well-established deubiquitinase, has been extensively implicated in the malignant progression of various human tumors. However, its role in head and neck squamous cell carcinoma (HNSC) requires further investigation. Here, we revealed that USP18 was significantly upregulated in HNSC and knockdown of USP18 markedly suppressed tumor growth in vivo. Furthermore, silencing USP18 attenuated HNSC cell proliferation, invasion, and migration, while overexpression of USP18 exerted converse effects. Mechanistically, USP18 diminished K48-linked ubiquitination of polo-like kinase 1 (PLK1) to stabilize the protein through its deubiquitinase activity. Subsequently, we validated that USP18 modulated PLK1 to activate the mTORC1 pathway, thereby facilitating HNSC cell proliferation, invasion, and migration. In conclusion, our findings demonstrate that elevated expression of USP18 in HNSC cells promotes tumorigenesis by regulating the PLK1-mTORC1 pathway.

Xeroderma Pigmentosum Type C Primary Skin Fibroblasts Overexpress HGF and Promote Squamous Cell Carcinoma Invasion in the Absence of Genotoxic Stress.

Xeroderma pigmentosum (XP) is a very rare recessive disease caused by the incapacity to resolve ultraviolet-induced DNA lesions through Nucleotide Excision Repair (NER). Most XP patients suffer from aggressive skin carcinoma and melanoma at a very early age (<8). Our previous results showed that primary XP fibroblasts isolated from healthy (non-photo-exposed) skin negatively impact the extracellular matrix and fail to activate the innate immune system. Here, we show for the first time that XP-C fibroblasts also play a major role in cancer cell invasion ex vivo and in vivo through the overexpression of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) in the absence of genotoxic attacks. The use of inhibitors of the activation of the HGF/SF pathway counteracted the effects of XP fibroblasts on the growth of cancer cells, suggesting new perspectives in the care of XP patients.

Betaine Induces Apoptosis and Inhibits Invasion in OSCC Cell Lines.

Betaine, known as trimethylglycine, is a non-toxic natural substance reported to affect cancer cell responses. This study delves into the impact of betaine on the survival, proliferation, and invasion of oral squamous cell carcinoma (OSCC) cells in vitro. Human OSCC cells (HSC-4 and HSC-7) were subjected to varying concentrations of betaine, and their viability and proliferation were assessed through colourimetric MTT and colony-forming unit assays. Cell cycle progression and cell apoptosis were also investigated using flow cytometry, while cell migration and invasion were examined using a transwell migration assay, and the mRNA expression was evaluated by a quantitative polymerase chain reaction. Finally, proteomic analysis was conducted through liquid chromatography-tandem mass spectrometry on the extracted protein component of the cells. Results indicate that betaine effectively suppressed OSCC proliferation and colony formation. It triggered early apoptosis without disrupting cell cycle progression, reduced cell migration, and inhibited invasion. Betaine exposure led to significantly decreased mRNA levels of MMP1, MMP2, and MMP9 while downregulating FN1, a gene linked to epithelial-to-mesenchymal transition. Proteomic analysis revealed 9240 differentially expressed up/downregulated proteins in cells treated with betaine. The significantly upregulated proteins were associated with ATP-binding cassette (ABC) transporters, while the down-regulated proteins were associated with G protein-coupled receptors (GPCR) ligand binding. In conclusion, betaine exhibits potent anti-cancer properties by attenuating OSCC cell proliferation and mitigating invasion. Exploring this natural product as an adjunct for managing oral squamous cell carcinoma shows promise, although further investigations are needed to fully elucidate its functionality.

The promotion of cell proliferation and invasion in cutaneous squamous cell carcinomas after ARNT downregulation is associated with CXCL3

The aryl hydrocarbon receptor nuclear translocator (ARNT) is a transcription factor associated with adaptive responses to cellular stress. Its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. The aim of this study was to investigate the role of ARNT in cSCC. Immunohistochemistry revealed downregulation of ARNT in cSCC, precancerous lesions (actinic keratosis), and cells. Knockdown of ARNT in A431 and SCL-1 cells significantly enhanced cell growth and metastasis. Microarray analysis and Ingenuity Pathway Analysis confirmed that loss of ARNT in A431 cells was highly correlated with cell growth and movement and upregulated CXCL3 expression. Cellular and xenograft experiments further confirmed that ARNT regulates cSCC proliferation and invasiveness in a CXCL3-dependent manner. ARNT may regulate CXCL3 expression through ROS-STAT3 pathway. In conclusion, this study demonstrates that ARNT plays a critical role in the development of cSCC and significantly affects the proliferation and metastatic ability of cSCC cells. It has the potential to serve as an ideal treatment target for cSCC.