Proliferation Of Squamous Cell Carcinoma Research Articles

DNA 6mA demethylase ALKBH1 regulates DDX18 expression to promote proliferation of human head and neck squamous cell carcinoma.

Human head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Currently, surgical resection plus a combination of chemotherapy and radiotherapy is the standard treatment for HNSCC, and the 5-year survival rate of patients with HNSCC remains very low because of the higher incidence of metastasis with consequent recurrence. Here, we aimed to investigate the potential role of DNA N6-methyladenine (6mA) demethylase ALKBH1 in tumor cell proliferation in HNSCC. The expression of ALKBH1 in 10 pairs of HNSCC/normal tissues and 3 HNSCC cell lines were measured by qRT‒PCR and western blotting. Colony formation, flow cytometry, patient-derived HNSCC organoid assays were used to assess the role of ALKBH1 in HNSCC cell proliferation in cell lines and human HNSCC patients. MeDIP-seq, RNA sequencing, Dot blotting and western blotting were used to evaluate the regulatory effect of ALKBH1 on the expression of DEAD-box RNA helicase DDX18. A dual-luciferase reporter assay was used to assess the putative effect of DNA 6mA levels on DDX18 transcription. ALKBH1 was highly expressed in HNSCC cells and patient tissues. Functional experiments revealed that ALKBH1 knockdown in SCC9, SCC25, and CAL27 cells inhibited their proliferation in vitro. Using patient-derived HNSCC organoid assay, we found that knockdown of ALKBH1 inhibited the proliferation and colony formation of HNSCC patients-derived organoids. Moreover, we found that ALKBH1 can enhance DDX18 expression by erasing DNA 6mA level and regulating its promoter activity. ALKBH1 deficiency blocked tumor cell proliferation by inhibiting DDX18 expression. Exogenous overexpression of DDX18 rescued the cell proliferation arrest caused by ALKBH1 knockdown. Our data reveal the important role of ALKBH1 in regulating proliferation of HNSCC.

Fusobacterium nucleatum promotes the early occurrence of esophageal cancer through upregulation of IL-32/PRTN3 expression.

Previous studies have shown that gastrointestinal microbiome is associated with the development of esophageal cancer, but the relationship and molecular mechanism between esophageal microbiota and the early development of esophageal cancer remain unclear. Here, we found that Lactobacillus, Escherichia-Shigella, Rikenellaceae-RC9-gut-group, Morganella, and Fusobacterium were more abundant in early-stage esophageal cancer (EEC) tissues compared with normal esophageal tissues. The abundance of bacteria such as Prevotella, Fusobacterium, Porphyromonas, Actinobacillus, and Neisseria in advanced esophageal cancer (AEC) was higher than that in EEC. Then, we further verified that Fusobacterium nucleatum (Fn) was enriched in EEC tissues and that its abundance increased with the progression of esophageal cancer by FISH and RT-PCR. Next, we demonstrated that Fn promoted the proliferation of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Finally, we confirmed that Fn promoted ESCC proliferation by upregulating the expression of interleukin (IL)-32/proteinase 3 (PRTN3) and then activating the PI3K/AKT signaling pathway. In conclusion, Fn promoted the early development of ESCC by upregulating the expression of IL-32/PRTN3 and thereby activating the PI3K/AKT signaling pathway. A better understanding of the molecular mechanism of Fn in early esophageal cancer may contribute to the development of early screening markers to diagnose ESCC and provide new targets for treatment.

OPN up-regulated proliferation and invasion of head and neck squamous cell carcinoma through the p38MAPK signaling pathway

Osteopontin (OPN) is aberrantly expressed in various tumors. However, its role and detailed mechanisms in head and neck squamous cell carcinoma (HNSCC) have not been extensively described. Expression of OPN in HNSCC was examined at the gene and protein levels. The effect of cell proliferation ability was examined by Cell Counting Kit-8, colony formation assay, cell invasiveness by Transwell assay, the effect of OPN on protein expression of Capase-3 and Bcl2 by Western blotting, and the expression of p38MAPK signaling pathway by p38MAPK inhibitor SB203580. We found that OPN expression was higher in human HNSCC tissues than in adjacent tissues. Osteopontin may regulate the proliferation and invasion of HNSCC cells through the p38-MAPK signaling pathway. Our study identifies an important role for OPN in HNSCC and further demonstrates that it may regulate the proliferation and invasion of HNSCC cells by activating the p38-MAPK signaling pathway. Osteopontin may be a promising prognostic and diagnostic indicator and a potential target for cancer therapy.

BST2 regulated by the transcription factor STAT1 can promote metastasis, invasion and proliferation of oral squamous cell carcinoma via the AKT/ERK1/2 signaling pathway.

Oral squamous cell carcinoma (OSCC) is one of the main types of head and neck squamous cell carcinoma. Although progress has been made in treating OSCC, it remains a threat to human health, and novel therapeutic strategies are needed to extend the lifespan of patients with OSCC. The present study, evaluated whether bone marrow stromal antigen2 (BST2) and STAT1 were potential therapeutic targets in OSCC. Small interfering RNA (siRNA) or overexpression plasmids were used to regulate BST2 or STAT1 expression. Western blotting and reverse transcription‑quantitative PCR were performed to assess changes in the protein and mRNA expression levels of signaling pathway components. The effects of BST2 and STAT1 expression changes on the migration, invasion and proliferation of OSCC cells were assessed using the scratch test assay, Transwell assay and colony formation assay invitro, respectively. Cell‑derived xenograft models were used to evaluate the impact of BST2 and STAT1 on the occurrence and development of OSCC invivo. Finally, it was demonstrated that BST2 expression was significantly upregulated in OSCC. Furthermore, it was demonstrated that high expression of BST2 in OSCC contributed to the metastasis, invasion and proliferation of OSCC cells. Moreover, it was demonstrated that the promoter region of BST2 was regulated by the transcription factor STAT1, and that the STAT1/BST2 axis could affect the behavior of OSCC via the AKT/ERK1/2 signaling pathway. Invivo studies also demonstrated that STAT1 downregulation inhibited OSCC growth by down‑regulating BST2 expression via the AKT/ERK1/2 signaling pathway.

HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway.

Laryngeal squamous cell carcinoma (LSCC) is an aggressive and lethal malignant neoplasm with extremely poor prognoses. Accumulating evidence has indicated that preferentially expressed antigen in melanoma (PRAME) is correlated with several kinds of cancers. However, there is little direct evidence to substantiate the biological function of PRAME in LSCC. The purpose of the current study is to explore the oncogenic role of PRAME in LSCC. PRAME expression was analyzed in 57 pairs of LSCC tumor tissue samples through quantitative real-time PCR, and the correlation between PRAME and clinicopathological features was analyzed. The result indicated that PRAME was overexpressed in the LSCC patients and correlated with the TNM staging and lymphatic metastasis. The biological functions and molecular mechanism of PRAME in LSCC progression were investigated through in vitro and in vivo assays. Functional studies confirmed that PRAME facilitated the proliferation, invasion, migration, and epithelial-mesenchymal transition of LSCC cells, and PRAME also promoted tumor growth in vivo. HDAC5 was identified as an upstream regulator that can affect the expression of PRAME. Moreover, PRAME played the role at least partially by activating PI3K/AKT/mTOR pathways. The above findings elucidate that PRAME may be a valuable oncogene target, contributing to the diagnosis and therapy of LSCC.

Proliferation-associated 2G4 P48 is stabilized by malignant T-cell amplified sequence 1 and promotes the proliferation of head and neck squamous cell carcinoma

Background/purposeProliferation-associated protein 2G4 (PA2G4) has alternative transcriptional and translational initiation. One dominant transcript ENST00000303305 could be translated into two protein isoforms (PA2G4-P42 and PA2G4-P48). In this study, we aimed to explore the effects of PA2G4-P42 and PA2G4-P48 on the proliferation of head and neck squamous cell carcinoma (HNSCC) and the mechanisms regulating PA2G4-P48 stability. Materials and methodsHNSCC cell lines HSC2 and SCC25 with relatively low PA2G4 expression were used for in-vitro cell studies. PA2G4-P42 and PA2G4-P48 overexpression lentiviruses were generated. In vitro cell proliferation was assessed by CCK-8 and colony formation. In vivo tumor cell proliferation was assessed by HSC2 cell-derived xenograft tumors. Liquid chromatography-mass spectrometry (LC-MS)/MS and co-immunoprecipitation (co-IP) assays were applied to check PA2G4-P48 interacting partners. Cycloheximide (CHX) chase and ubiquitin-based co-IP assays were also performed. ResultsPA2G4-P48 was the dominant isoform, with substantially higher expression than PA2G4-P42 in HNSCC. PA2G4-P48 overexpression enhanced HNSCC cell proliferation, but PA2G4-P42 overexpression slowed the proliferation. MCTS1 interacted with PA2G4-P48, but not PA2G4-P42. PA2G4 protein but not its mRNA expression was decreased in cells with MCTS1 knockdown. MG132 treatment abrogated this alteration. MCTS1 overexpression significantly elevated the half-life of PA2G4-P48, while its knockdown drastically reduced the half-life compared with the control cells. In addition, MCTS1 overexpression significantly decreased the polyubiquitination of exogenous flag-tagged PA2G4-P48. MCTS1 overexpression-induced cell proliferation was hampered by knocking down of PA2G4-P48. ConclusionPA2G4-P42 and PA2G4-P48 exert growth-suppressive and growth-promoting effects in HNSCC, respectively. MCTS1 can interact with PA2G4-P48 and prolong its half-life by reducing its poly-ubiquitination.

Comprehensive analysis ofCDK5 as a novel biomarker for progression in esophageal cancer.

Cyclin-dependent kinase 5 (CDK5) is a member of the cyclin-dependent kinase family, and unlike the rest of the members of the family, its kinase activity is independent of cyclins. Accumulating evidence has shown that CDK5 plays a significant role in the progress of tumorigenesis except in nervous system. In particular, the expression of CDK5 and its function in esophageal cancer (ESCA) remain unknown. With TCGA and GEO databases, CDK5 was analyzed with the expression, predicted value, clinical relationship, functional enrichment, immune cell infiltration and immune molecules in ESCA. In addition, we explored the CDK5 expression with local datasets and the influence of CDK5 on proliferation, migration and invasion behaviors of the esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo experiments. CDK5 expression was upregulated in ESCA, and this regulation has been verified in cell lines of ESCC. Further analysis has found that the expression of CDK5 was correlated with race, weight, BMI, histological type and tumor central location in ESCA. KEGG analysis revealed that CDK5 was involved in the progress of cancers, innate immune system and PI3K-Akt signaling pathway. CDK5 was closely related to immune cells and immune molecules in ESCA. Functional experiments confirmed CDK5 was an oncogene in ESCC by in vivo and in vitro models. This study shows that CDK5 is a risk factor to promote tumor progression, and Roscovitine could be one of the effective tools in the therapy of ESCA.

Fucoxanthin inhibits the proliferation and stem cell formation of oral squamous cell carcinoma (OSCC) cells by regulating JAK/STAT3 pathway

Purpose: To investigate the effect and regulatory mechanism of fucoxanthin (FX) on oral squamous cell carcinoma (OSCC).
 Methods: Human OSCC SCC9 and Cal27 cells were treated with different concentrations of FX (7.5, 15, and 30 μM) to determine cell viability, number of colonies, and apoptosis rate using methyl thiazolyl diphenyl-tetrazolium bromide (MTT) assay, crystal violet staining, and flow cytometry, respectively. In addition, the number of spheres of OSCC cells was determined by a cell sphere-forming assay. The stem cells and levels of pathway-related proteins were evaluated by western blotting.
 Results: Fucoxanthin decreased SCC9 and Cal27 cell viability and the number of colonies, but increased apoptosis in a dose-dependent manner. The expression levels of SOX2 and POU5F1 were down-regulated, while the number of spheres was reduced in SCC9 and Cal27 cells treated with 7.5 or 15 μM of FX (p < 0.05). Moreover, FX attenuated p-JAK/JAK and p-STAT3/STAT3 expression levels in a dose-dependent manner (p < 0.05).
 Conclusion: Fucoxanthin accelerates apoptosis and inhibits cell mobility and OSCC stem cell formation by suppressing JAK/STAT3 pathway in OSCC, thus providing an experimental basis for research on the anti-tumor effect of kelp extract and the development of new drugs from marine plants.

GOLM1 affects proliferation, invasion, and migration by regulating Wnt pathway in esophageal squamous cell carcinoma cells

AimTo investigate the effect of Golgi membrane protein 1 (GOLM1) on the proliferation, migration, and invasion of esophageal squamous cell carcinoma (ESCC) cells and its underlying oncogenic mechanism. MethodsThe Expression level of GOLM1 in esophageal cancer (EC) tissues were analyzed in the cancer genome database. Fresh ESCC tissues and cancer adjacent tissues of 44 patients with EC who underwent radical esophagectomy were collected. GOLM1 mRNA expression was detected by RT qPCR. ESCC cell lines (EC9706, TE-1, Eca-109, kyse-150) and normal esophageal epithelial cells (HEEC) were cultured in vitro. ResultsThe expression level of GOLM1 in EC tissues was significantly higher (P < 0.05). The mRNA expression level of GOLM1 in ESCC was significantly higher than that in adjacent tissues (P < 0.05). Compared with HEEC cells, the mRNA and protein expression levels of GOLM1 in ESCC cell lines were significantly higher (P < 0.05). Kyse-150 cells showed the highest expression of GOLM1. Kyse-150 cells were divided into control group, lenti-NC group, GOLM1 overexpression group, SH-NC group, GOLM1 silencing group, XAV -939 group, and GOLM1 overexpression + XAV -939 group. After lentivirus transfection, the expression levels of mRNA and protein of GOLM1 were significantly higher (P＜0.05). In the GOLM1 silence group, all these variables were significantly decreased. Overexpression of GOLM1 can increase the expression of Wnt3a and nuclear β-catenin and can reverse the effect of XAV-939 intervention. The effect of GOLM1 silence was consistent with that of the XAV-939 intervention. Compared with the NC group, the tumor volume and tumor index of the GOLM1 knockdown group decreased significantly in vivo (P < 0.05). ConclusionGOLM1 is up-regulated in ESCC tissues and ESCC cells and may function as an oncogene. GOLM1 silencing can reduce the proliferation, migration, and invasion of ESCC cells by inhibiting Wnt/β-catenin signaling pathway.

ACTN1 interacts with ITGA5 to promote cell proliferation, invasion and epithelial-mesenchymal transformation in head and neck squamous cell carcinoma.

The aim of this study was to detect the expression levels of α-Actinin 1 (ACTN1) and ITGA5 in HNSCC and to explore how ACTN1/ITGA5 regulated the proliferative and invasive abilities, as well as the EMT of Head and neck squamous cell carcinoma (HNSCC) cells. The viability, proliferative, invasive and migrative abilities of HNSCC cells after transfection were, in turn, detected by CCK8 assay, colony formation assay, EdU staining, transwell, as well as wound healing. E-cadherin in transfected cells was assessed utilizing immunofluorescence. RT-qPCR confirmed the transfection effect of ACTN1 and ITGA5 in HNSCC cells and the interaction between ACTN1 and ITGA5 in HNSCC cells was determined by co-immunoprecipitation (Co-IP). With Western blot application, the contents of ACTN1, ITGA5, proliferation-, invasion- and migration-related proteins were estimated. A xenograft model based on nude mice was conducted and Ki-67 content in tumor tissues was evaluated employing immunohistochemistry (IHC) staining. ACTN1 interacted with ITGA5. The contents of ACTN1 and ITGA5 were found to be abundant in HNSCC tissues and cells and associated with poor prognosis. ACTN1 depletion imparted suppressive impacts on cell proliferative, invasive and migrative abilities as well as EMT of HNSCC cells, which were reversed by ITGA5 overexpression. In addition, ACTN1 deficiency repressed the growth and metastasis of tumor tissues in tumor xenografts of nude mice. ACTN1 positively interacts with ITGA5 to promote proliferation, invasion and EMT of HNSCC cells. Also, ACTN1 promotes tumor growth and metastasis.

Comprehensive Analysis Reveals Distinct Immunological and Prognostic Characteristics of CD276/B7-H3 in Pan-Cancer.

CD276 (also known as B7-H3), a newly discovered immunoregulatory protein that belongs to the B7 family, is a significant and attractive target for cancer immunotherapy. Existing evidence demonstrates its pivotal role in the tumorigenesis of some cancers. However, there still lacks a systematic and comprehensive pan-cancer analysis of the role of CD276 in tumor immunology and prognosis. We explored and validated the mRNA and protein expression levels of CD276 in multiple tumors through public databases and clinical tissues specimens. The Univariate Cox regression analysis and Kaplan-Meier analysis were applied to assess the prognostic value of CD276. The correlation between CD276 expression and clinical characteristics and immunological features in diverse tumors was also explored. GSEA was performed to illuminate the biological function and involved pathways of CD276. Moreover, the CellMiner database was used to interpret the relationship between CD276 and multiple chemotherapeutic agents. CCK-8 assay was performed to validate the biological function of CD276 in vitro. In general, CD276 was differentially expressed between most tumor tissues and their corresponding normal tissues. Higher expression levels of CD276 were associated with poorer survival outcomes in most tumor cohorts from TCGA. There was a close correlation between CD276 expression and clinical features, the infiltration levels of specific immune cells, immune subtypes, TMB, MSI, MMR, recognized immunoregulatory genes and drug sensitivity across diverse human cancers. The scRNA-seq data analysis further revealed that CD276 was mainly expressed on the tumor infiltrating macrophages. Additionally, in vitro experiments showed that knockdown of CD276 inhibited the proliferation of ovarian cancer (OV) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) cell lines. CD276 is a potent biomarker for predicting the prognosis and immunological features in some tumors, and it may play a critical role in the tumor immune microenvironment (TIME) through macrophage-associated signaling.

Circular RNA circTRPS1-2 inhibits the proliferation and migration of esophageal squamous cell carcinoma by reducing the production of ribosomes

Circular RNAs play important roles in many cancers, including esophageal squamous cell carcinoma (ESCC), but the precise functions of most circular RNAs are poorly understood. Here we detected significant downregulation of circTRPS1-2 in ESCC based on high-throughput sequencing of three pairs of ESCC tissue and adjacent normal tissue, followed by PCR validation with another 30 tissue pairs. Patients with ESCC whose circTRPS1-2 expression was below the median level for the sample showed significantly shorter median overall survival (13 months) than patients whose circTRPS1-2 expression was above the median (36 months). Overexpressing circTRPS1-2 in the human ESCC cell lines K150 and E109, which express low endogenous levels of circTRPS1-2, inhibited cell proliferation and migration. Conversely, knocking down circTRPS1-2 using short interfering RNA promoted cell proliferation and migration. Similar results were observed in mice bearing K150 xenografts in which circTRPS1-2 was overexpressed or knocked down. Several ribosomal proteins co-immunoprecipitated with circTRPS1-2 from K150 cells in culture, and K150 cells overexpressing circTRPS1-2 showed reduced numbers of ribosomes by A260 absorbance measure and electron microscopy. Our results suggest that circTRPS1-2 can inhibit ESCC proliferation and migration by reducing the production of ribosomes, establishing its potential usefulness in ESCC treatment and prediction of prognosis.

Ferroportin depletes iron needed for cell cycle progression in head and neck squamous cell carcinoma.

Ferroportin (FPN), the only identified eukaryotic iron efflux channel, plays an important role in iron homeostasis and is downregulated in many cancers. To determine if iron related pathways are important for Head and Neck Squamous Cell Carcinoma (HNSCC) progression and proliferation, we utilize a model of FPN over-expression to simulate iron depletion and probe associated molecular pathways. The state of iron related proteins and ferroptosis sensitivity was assessed in a panel of metastatic HNSCC cell lines. Stable, inducible expression of FPN was confirmed in the metastatic HNSCC lines HN12 and JHU-022 as well as the non-transformed normal oral keratinocyte (NOK) cell line and the effect of FPN mediated iron depletion was assessed in these cell lines. HNSCC cells are sensitive to iron chelation and ferroptosis, but the non-transformed NOK cell line is not. We found that FPN expression inhibits HNSCC cell proliferation and colony formation but NOK cells are unaffected. Inhibition of cell proliferation is rescued by the addition of hepcidin. Decreases in proliferation are due to the disruption of iron homeostasis via loss of labile iron caused by elevated FPN levels. This in turn protects HNSCC cells from ferroptotic cell death. Expression of FPN induces DNA damage, activates p21, and reduces levels of cyclin proteins thereby inhibiting cell cycle progression of HNSCC cells, arresting cells in the S-phase. Induction of FPN severely inhibits Edu incorporation and increased β-galactosidase activity, indicating cells have entered senescence. Finally, in an oral orthotopic mouse xenograft model, FPN induction yields a significant decrease in tumor growth. Our results indicate that iron plays a role in HNSCC cell proliferation and growth and is important for cell cycle progression. Iron based interventional strategies such as ferroptosis or iron chelation may have potential therapeutic benefits in advanced HNSCC.

Inhibition of human oral squamous cell carcinoma proliferation and migration by prodrug-activating suicide gene therapies.

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.

LINC01232 Facilitates the Proliferation of Esophageal Squamous Cell Carcinoma by Sponging miR-708-5p to Upregulate Upstream Stimulatory Factor 1

LncRNAs are vital regulators in human diseases. LINC01232 is found to be upregulated in esophageal squamous cell carcinoma (ESCC). This study aims to uncover the biological functions of LINC01232 in the development of ESCC and the underlying mechanism. Expression pattern of LINC01232 and its influence on the prognosis in ESCC were determined by analyzing the dataset downloaded from TCGA. LINC01232 levels in ESCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Regulatory effects of LINC01232 on proliferative and apoptotic abilities in ESCC were examined by Cell Counting Kit (CCK-8) assay, colony formation assay and flow cytometry, respectively. The interaction in the LINC01232/miR-708-5p/USF1 axis was tested by dual-luciferase reporter assay. By analyzing ESCC profiling downloaded from TCGA, LINC01232 was found to be upregulated in ESCC tissues, while its level was unrelated to overall survival and disease-free survival in ESCC patients. LINC01232 was further confirmed to be highly expressed in ESCC tissues and cell lines we collected. Knockdown of LINC01232 inhibited proliferative ability and induced apoptosis in ESCC cells. LINC01232 competed with USF1 to bind miR-708-5p, and thereafter regulated the development of ESCC. LINC01232/miR-708-5p/USF1 axis is responsible for facilitating the proliferative ability in ESCC, thereby aggravating the malignant development of ESCC.

Retracted: COQ10B Knockdown Modulates Cell Proliferation, Invasion, Migration, and Apoptosis in Esophageal Squamous Cell Carcinoma.

[This retracts the article DOI: 10.1155/2022/6247824.].

Targeted Knockdown of Macrophage Migration Inhibitory Factor Enhances UVB Irradiation-Induced Apoptosis Via Increasing ROS Generation in Oral Squamous Cell Carcinoma.

Objectives: We investigated the effects of macrophage migration inhibitory factor (MIF) knockdown or overexpression combined with ultraviolet radiation B (UVB) irradiation on cell proliferation and apoptosis of oral squamous cell carcinoma (OSCC). Methods: MIF expression in OSCC and adjacent tissues was detected by immunohistochemistry. MIF expression in human immortalized oral epithelial cells (HIOEC) and OSCC cells was detected by western blotting. MIF was knocked down or overexpressed in OSCC cell lines (SCC-25 and CAL-27). OSCC cells were set up into control (CON), MIF overexpression/knockdown (oeMIF/shMIF), CON + UVB, and oeMIF + UVB/shMIF + UVB groups based on their exposure to UVB irradiation. Cell line proliferation was studied using a cell counting kit-8 (CCK-8) and colony formation assays. Flow cytometry was applied for determination of apoptosis, cell cycle, reactive oxygen species (ROS) abundance, and mitochondrial membrane potential. Apoptosis-related proteins were assayed by western blotting. Results: The expression of MIF was significantly higher in OSCC tissues and cell lines than in adjacent tissues and HIOEC. MIF knockdown accompanied by UVB irradiation significantly hampered cell viability and proliferation compared to MIF knockdown or UVB irradiation alone. Western blotting and flow cytometry showed that MIF knockdown combined with UVB irradiation not only induced apoptosis via the mitochondrial pathway but also mediated the cell cycle. Flow cytometry showed that ROS and mitochondrial membrane potential depolarization were increased in the combination treatment groups compared with the mono-treatment groups. Additionally, the ROS scavenger N-acetylcysteine significantly attenuated MIF knockdown combined with UVB irradiation-induced apoptosis and reversed MIF knockdown combined with UVB irradiation-induced MAPK activation. Conclusion: MIF knockdown combined with UVB irradiation significantly inhibited the proliferation of OSCC cells. MIF was involved in UVB-induced ROS generation and enhanced UVB irradiation-induced mitochondria-dependent apoptosis of OSCC cells by activating the MAPK pathway. This suggests that MIF-targeted therapy combined with UVB irradiation may be a novel approach for treating OSCC.

Retracted: Biogenic Analysis of the Effect of TERC on Cell Proliferation and Migration of Oral Squamous Cell Carcinoma under Digital Minimally Invasive Treatment.

[This retracts the article DOI: 10.1155/2022/2102795.].

Podoplanin promotes cell proliferation, survival, and migration of canine non-tonsillar squamous cell carcinoma.

Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.

HOXA5 inhibits the proliferation and metastasis of cervical squamous cell carcinoma by suppressing the β-catenin/Snail signaling.

HOXA5, as a transcription factor, plays an important role in a variety of malignant tumors. Nevertheless, its biological role in cervical squamous cell carcinoma (CSCC) is largely unknown. In our study, we aimed to explore the function of HOXA5 in CSCC and its molecular mechanism. Immunohistochemistry showed that HOXA5 expression was downregulated in human CSCC tissues and HOXA5 staining was negatively correlated with tumor size and histological grade of CSCC. Ectopic expression of HOXA5 inhibited proliferative and metastatic abilities of CSCC cells in vitro and in vivo. Furthermore, overexpression of HOXA5 inhibited the cell cycle by arresting the S/G2 phase by flow cytometry and that was related to the downregulation of Cyclin A. Further study showed that HOXA5 suppressed EMT by inhibiting the β-catenin/Snail signaling resulting in reduced metastasis of CSCC cells. Altogether, our results suggested that HOXA5 inhibited the proliferation and metastasis via repression of the β-catenin/Snail pathway, proposing the potential role of HOXA5 in the prevention and treatment of CSCC.