Progression Of Squamous Cell Carcinoma Research Articles

DEAD/H-box helicase 11 is transcriptionally activated by Yin Yang-1 and accelerates oral squamous cell carcinoma progression.

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. DEAD/H-box helicase 11 (DDX11), a DNA helicase, has been implicated in the progression of several cancers. Yet, the precise function of DDX11 in OSCC is poorly understood. The DDX11 expression in OSCC cells and normal oral keratinocytes was evaluated in the Gene Expression Omnibus database (GSE146483 and GSE31853). SCC-4 and CAL-27 cells expressing doxycycline-inducible DDX11 or DDX11 shRNA were generated by lentiviral infection. The role of DDX11 in OSCC cells was determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry assay, TUNEL staining, and western blot. The effects of DDX11 on tumor growth were explored in a xenograft nude mouse model. The relationship between DDX11 and transcription factor Yin Yang-1 (YY1) was researched using the dual luciferase report assay and chromatin immunoprecipitation assay. DDX11 expression was significantly upregulated in OSCC cells. Knockdown of DDX11 inhibited cell proliferation, induced cell cycle arrest, and suppressed PI3K-AKT pathway, while DDX11 overexpression showed opposite effects. The number of apoptotic cells was increased in DDX11 silenced cells. DDX11 upregulation or knockdown accelerated or suppressed tumor growth in vivo, respectively. Moreover, the YY1 bound and activated the DDX11 promoter, resulting in increasing DDX11 expression. Forced expression DDX11 reversed the anticancer effects of YY1 silencing on OSCC cells. DDX11 has tumor-promoting function in OSCC and is transcriptionally regulated by YY1, indicating that DDX11 may serve as a potential target for the OSCC treatment.

The role of AGAP2-AS1, DLEU2, HMBOX1_1, and UGDH-AS1 in the progression of esophageal squamous cell carcinoma

Abstract Background Long noncoding RNAs (lncRNAs) have been recognized as viable prognostic and therapeutic indicators for numerous human malignancies. Nonetheless, the operational roles and fundamental mechanisms of important lncRNAs that impact esophageal squamous cell carcinoma (ESCC) remain predominantly obscure. Recently, lncRNAs have been identified to exert regulatory influence on epithelial-mesenchymal transition (EMT) via intricate interplay with EMT-associated transcription factors (TFs) and signaling pathways. The current experimental study aimed to elucidate the expression of four lncRNAs in ESCC patients and explain their potential involvement in the EMT process and the pathogenesis of ESCC. Methods In the study, the expression levels of lncRNAs (AGAP2-AS1, DLEU2, HMBOX1_1 (AC108449.2), and UGDH-AS1) and mRNAs (TWIST1, MMP13, and CD44S) between fifty ESCC and adjacent normal tissue samples were measured using quantitative real-time PCR. Results The upregulation of CD44S (36%), TWIST1 (52%), DLEU2 (58%), AGAP2-AS1 (62%), and MMP13 (74%), were indicated in ESCC samples, while the downregulation of UGDH-AS1 and HMBOX1_1 were found in 62% and 64% of patients, respectively. The expression levels of lncRNAs and EMT-related markers were found to be significantly correlated in several patient clinicopathological traits (P < 0.05), representing correlations between AGAP2-AS1, DLEU2, HMBOX1_1 (AC108449.2), and UGDH-AS1 with EMT status in ESCC. Conclusion Our results have unveiled that these lncRNAs, which regulate EMT, may play a crucial role in the regulatory process of EMT via the CD44S-TWIST1-MMP13 axis. Moreover, it may be assumed that lncRNAs present a promising avenue for both diagnosis and therapeutic intervention in the context of ESCC.

Development and Validation of Machine Learning Models for Predicting Tumor Progression in OSCC.

Development of a prediction model using machine learning (ML) method for tumor progression in oral squamous cell carcinoma (OSCC) patients would provide risk estimation for individual patient outcomes. This predictive modeling study was conducted of 1163 patients with OSCC from Hospital of Stomatology, SYSU and SYSU Cancer Center from March 2009 to October 2021. Clinical, pathological, and hematological features of the patients were collected. Six ML algorithms were explored, and model performance was assessed by accuracy, sensitivity, specificity, f1 score, and AUC. SHAP values were used to identify the variables with the greatest contribution to the model. Among the 1163 patients (mean [SD] age, 55.36 [12.91] years), 563 are from development cohort and 600 are from validation cohort. The Logistic Regression algorithm outperformed all other models, with a sensitivity of 94.7% (68.2%), a specificity of 55.3% (63.7%), and the AUC of 0.76 ± 0.09 (0.723) in the development (validation) cohort. The most predictive feature was neutrophil count. This study demonstrated ML models can improve clinical prediction of oral squamous cell carcinoma progression through basic information of patients. These tools could be used to provide individual risk estimation and may help direct intervention.

The impact of ERP29 on the progression of pharyngeal squamous cell carcinoma

ERP29 gene encodes a chaperone protein critical for protein folding and secretion. Previous study linked ERP29 inhibition to an elevated risk of pharynx squamous cell carcinoma (PSCC) and reduced patients’ survival. However, ERP29 role in PSCC progression remains unknown. Here, we investigated ERP29 impact on PSCC progression in cisplatin (CDDP)-sensitive (FaDu and LAU-2063), CDDP-treated (FaDu-CDDP), and CDDP-resistant (FaDu-R) cells. ERP29 silencing decreased necrosis and increased migration in CDDP-sensitive, treated, and resistant cells; and reduced E-cadherin and increased vimentin immunoexpression in CDDP-sensitive 3D-spheroids. During CDDP treatment, ERP29 silencing enhanced proliferation. In CDDP-sensitive cells, ERP29 silencing upregulated genes associated with WNT, MAPK, and PI3K/AKT signaling pathways while downregulating CASP9 expression. During CDDP treatment, ERP29 silencing downregulated MDM2 and CASP9 expression. In CDDP-resistant cells, ERP29 silencing upregulated SOS1, MAPK1, AKT1, ITGAV, and CCNE1, while downregulating KRAS, JUN, MDM2, and CASP9 expression. In addition, inhibition of microRNA miR-4421 increased ERP29 expression and decreased MAPK1, AKT1, and JUN expression in CDDP-sensitive cells, as well as SOS1, MAPK1, AKT1, and ITGAV in CDDP-resistant cells. Lower ERP29 and higher miR-4421 expressions were predictive of poor survival, suggesting a potential therapeutic use for miR-4421 inhibitors. Upon validation, these findings may contribute to targeted therapies for PSCC based on ensuring ERP29 expression.

Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.

Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.

Prolonged Survival of Neutrophils Induced by Tumor-Derived G-CSF/GM-CSF Promotes Immunosuppression and Progression in Laryngeal Squamous Cell Carcinoma.

Tumor-associated neutrophils (TANs) play a crucial role in tumor progression and exhibit prolonged survival. However, the mechanism underlying their extended lifespan and significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. Herein, it is observed that apoptosis of TANs is significantly delayed owing to induction by tumor-derived G-CSF and GM-CSF through the activation of the PI3K-AKT signaling pathway, upregulation of anti-apoptotic Mcl-1 expression, and downregulation of activated Caspase-3 levels. It is found that prolonged survival of TANs leads to the accumulation of aged CXCR4+ neutrophils that exhibit potent immunosuppressive properties and are associated with poor patient prognosis. Furthermore, extended survival promotes the enhanced immunosuppressive function of CD8+ T cells by TANs, thereby facilitating the in vitro and in vivo progression and growth of human LSCC tumors. Importantly, this effect could be reversed by blocking G-CSF and GM-CSF stimulation of neutrophils. These findings elucidate the pivotal role of pathologically prolonged neutrophil survival in impairing CD8+ T cell immunity and suggest targeting it as a potential therapeutic strategy for tumors.

MicroRNA‑374a‑5p/ANLN axis promotes malignant progression of Oral squamous cell carcinoma

Background: Recent research has revealed a significant association between Anillin (ANLN) and miR-374a‑5p with the progression of tumors. Additionally, bioinformatics analysis indicated an inverse relationship in transcript expression levels between ANLN and miR-374a-5p. However, the specific mechanisms driving the miR-374a-5p/ANLN signaling axis in oral squamous cell carcinoma (OSCC) have not been thoroughly explored. Methods: ANLN and miR-374a‑5p expression were evaluated within OSCC cell lines and tissues by RT-qPCR. Using bioinformatics databases, it has been demonstrated that the ANLN gene could be a target of miR-374a-5p. MiR-374a‑5p and ANLN correlation could be assessed via the dual-luciferase reporter assay and western blotting techniques. Functional studies were employed to investigate the behavioral patterns of miR-374a‑5p within OSCC cells. Results: miR-374a‑5p expression could be remarkably downregulated within both OSCC tissues and cells, coinciding with high ANLN expression. ANLN was a specific target gene for miR-374a‑5p by luciferase function assay. The expression of miR-374a‑5p could serve as a diagnostic biomarker and independently predict a poor prognosis in patients with OSCC, and the counteractive effect of upregulating miR-374a‑5p was observed on the proliferative, migratory, and invasive capabilities of OSCC cells. Conclusions: The findings suggest that the miR-374a‑5p/ANLN signaling axis potentially modulates the advancement of OSCC, and miR-374a‑5p may serve as potential therapeutic targets of oral cancer.

AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.

HPV16 integration regulates ferroptosis resistance via the c-Myc/miR-142-5p/HOXA5/SLC7A11 axis during cervical carcinogenesis

BackgroundFerroptosis, a newly identified form of regulated cell death triggered by small molecules or specific conditions, plays a significant role in virus-associated carcinogenesis. However, whether tumours arising after high-risk HPV integration are associated with ferroptosis is unexplored and remains enigmatic.MethodsHigh-risk HPV16 integration was analysed by high­throughput viral integration detection (HIVID). Ferroptosis was induced by erastin, and the levels of ferroptosis were assessed through the measurement of lipid-reactive oxygen species (ROS), malondialdehyde (MDA), intracellular Fe2+ level and transmission electron microscopy (TEM). Additionally, clinical cervical specimens and an in vivo xenograft model were utilized for the study.ResultsExpression of HPV16 integration hot spot c-Myc negatively correlates with ferroptosis during the progression of cervical squamous cell carcinoma (CSCC). Further investigation revealed that the upregulated oncogene miR-142-5p in HPV16-integrated CSCC cells served as a critical downstream effector of c-Myc in its target network. Inhibiting miR-142-5p significantly decreased the ferroptosis-suppressing effect mediated by c-Myc. Through a combination of computational and experimental approaches, HOXA5 was identified as a key downstream target gene of miR-142-5p. Overexpression of miR-142-5p suppressed HOXA5 expression, leading to decreased accumulation of intracellular Fe2+ and lipid peroxides (ROS and MDA). HOXA5 increased the sensitivity of CSCC cells to erastin-induced ferroptosis via transcriptional downregulation of SLC7A11, a negative regulator of ferroptosis. Importantly, c-Myc knockdown increased the anti-tumour activity of erastin by promoting ferroptosis both in vitro and in vivo.ConclusionsCollectively, these data indicate that HPV16 integration hot spot c-Myc plays a novel and indispensable role in ferroptosis resistance by regulating the miR-142-5p/HOXA5/SLC7A11 signalling axis and suggest a potential therapeutic approach for HPV16 integration-related CSCC.

Multi-omics reveals lactylation-driven regulatory mechanisms promoting tumor progression in oral squamous cell carcinoma

BackgroundLactylation, a post-translational modification, is increasingly recognized for its role in cancer progression. This study investigates its prevalence and impact in oral squamous cell carcinoma (OSCC).ResultsImmunohistochemical staining of 81 OSCC cases shows lactylation levels correlate with malignancy grading. Proteomic analyses of six OSCC tissue pairs reveal 2765 lactylation sites on 1033 proteins, highlighting its extensive presence. These modifications influence metabolic processes, molecular synthesis, and transport. CAL27 cells are subjected to cleavage under targets and tagmentation assay for accessible-chromatin with high-throughput sequencing, and transcriptomic sequencing pre- and post-lactate treatment, with 217 genes upregulated due to lactylation. Chromatin immunoprecipitation-quantitative PCR and real-time fluorescence quantitative PCR confirm the regulatory role of lactylation at the K146 site of dexh-box helicase 9 (DHX9), a key factor in OSCC progression. CCK8, colony formation, scratch healing, and Transwell assays demonstrate that lactylation mitigates the inhibitory effect of DHX9 on OSCC, thereby promoting its occurrence and development.ConclusionsLactylation actively modulates gene expression in OSCC, with significant effects on chromatin structure and cellular processes. This study provides a foundation for developing targeted therapies against OSCC, leveraging the role of lactylation in disease pathogenesis.

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

Differential molecular characterization of human papillomavirus-associated oropharyngeal squamous cell carcinoma and its prognostic value.

Human papillomavirus (HPV) infection is a causative factor in the occurrence and progression of oropharyngeal squamous cell carcinoma (OPSCC). In recent years, clinical studies have found that HPV-positive OPSCC patients may present a better prognosis than HPV-negative patients, yet the underlying causes are unclear. This study aimed to investigate the relevance of HPV infection and the prognosis of OPSCC. On this basis, we aimed to establish a prediction model to accurately predict the prognosis and guide clinical practice. We analysed the records of 233 patients with OPSCC. Cox regression was applied to identify factors associated with survival. Moreover, variables with significant discrepancies were integrated into a nomogram model to predict prognosis. The results showed that HPV was an independent prognostic factor for OS and PFS. Immunoglobulin Heavy Constant Mu (IGHM) mRNA was significantly upregulated in patients with HPV-positive OPSCC. Crucially, IGHM expression was associated with better prognosis. The receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis both confirmed that the prognostic model exhibits good performance. In summary, HPV infection were independent prognostic factors for OPSCC. IGHM may be the key contributors to the prognostic differences in HPV-associated OPSCC. This nomogram model was able to accurately predict the prognosis of patients.

The activation of asparagine synthetase by the transcription factor FOXM1 plays a pivotal role in the initiation and progression of ESCC.

This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.

LncRNA NR2F2-AS1 inhibits the progression of oral squamous cell carcinoma by mediating the miR-32-5p/SEMA3A axis.

Previous studies have supported a tumor-suppressive role of semaphorin 3A (SEMA3A) in several tumors including oral squamous cell carcinoma (OSCC). However, in-depth characterization of the role of SEMA3A in OSCC and the underlying molecular mechanisms is lacking. Gene and protein expressions were detected using quantitative real-time PCR, western blot assay, and immunohistochemistry. OSCC cell metastasis was evaluated using Transwell and angiogenesis of human umbilical vein endothelial cells (HUVECs) was determined using tube formation assay. The interactions among molecules were predicted using bioinformatics analysis and validated using luciferase activity experiment and RNA immunoprecipitation assay. Pulmonary metastasis was evaluated using hematoxylin and eosin staining after constructing a lung metastasis tumor model in mice. SEMA3A expression was decreased in OSCC cells and its overexpression led to suppression of epithelial-mesenchymal transition (EMT), migration, and invasion of OSCC cells and angiogenesis of HUVECs. miR-32-5p was identified as an upstream molecule of SEMA3A and long non-coding RNA NR2F2 antisense RNA 1 (NR2F2-AS1) was validated as an upstream gene of miR-32-5p. Further experiments revealed that the inhibitory effects of NR2F2-AS1 overexpression on EMT, migration, invasion of OSCC cells, and angiogenesis of HUVECs as well as tumor growth and metastasis in mice were mediated via the miR-32-5p/SEMA3A axis. To conclude, NR2F2-AS1 may attenuate OSCC cell metastasis and angiogenesis of HUVECs and suppress tumor growth and metastasis in mice via the miR-32-5p/SEMA3A axis.

Microbial Dysbiosis and Immunopathogenesis of Oral Microbiome in the Development and Progression of Oral Squamous Cell Carcinoma: Systematic Review

Objective: The purpose of this review is to evaluate the specific bacterial species and their association with oral cancer, particularly in oral squamous cell carcinoma (OSCC). Methodology: A literature search was done through PubMed, Scopus, and Web of Science databases, and data were extracted according to inclusion criteria. Original studies of 20 articles were included in this review. Results: A total of 20 articles and 961 samples were included in this review. The mean age was 60.12 ± 7.63, with a significantly higher male predilection (M: F – 2:1) ratio. 16S rRNA sequencing was found to be the most commonly used detection method. Alteration in the oral microbiome was seen with varying degrees of epithelial dysplasia, early & late stages of oral cancer. In OSCC patients, there was an increased abundance of specific microbiomes like Fusobacterium species, Porphyromonas gingivalis, and Prevotella compared to other species. Conclusion: From this systematic review, it has been found that the changes in diversity of oral microbiome in cancerous patients than that of healthy patients. In OSCC there is an increased abundance of specific species such as Fusobacterium species, Porphyromonas gingivalis, and Prevotella species.

Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase

Head and neck squamous cell carcinoma (HNSCC) present a significant challenge due to its heterogeneity and limited treatment options, often resulting in severe side effects and poor survival rates with conventional chemoradiotherapy. Here, we investigated the anticancer activity of halogenated benzoate derivatives of cleistanthin A, ECDD-S16 and ECDD-S18, in HNSCC cells. Our findings revealed that ECDD-S18 exhibited remarkable cytotoxicity, surpassing that of cisplatin with minimal impact on normal and cisplatin-sensitive cells. Notably, ECDD-S18 induced apoptosis in a dose-dependent manner and effectively targeted vacuolar ATPase (V-ATPase), impairing lysosomal acidification. Intriguingly, ECDD-S18 inhibited autophagic flux, as evidenced by increased autophagosome but decreased autolysosome formation. Furthermore, proteomic analysis demonstrated downregulation of cathepsin D (CTSD), the lysosomal protease in ECDD-S18-treated HNSCC cells, concurrent with suppressed cell migration. ECDD-S18 also decreased expression of mesenchymal markers, suggesting inhibition of epithelial-mesenchymal transition (EMT). Importantly, cotreatment with ECDD-S18 and cisplatin enhanced the reduction in cell viability. Collectively, our results indicated that the anticancer activity of ECDD-S18 partly stems from its ability to disrupt lysosomal acidification and inhibit autophagy via targeted inhibition of V-ATPase. These findings underscore the therapeutic promise of ECDD-S18 in HNSCC treatment, either alone or in combination with existing drugs, while mitigating toxicity to normal cells.

The role of cornulin (CRNN) in the progression of cutaneous squamous cell carcinoma involving AKT activation in SCL-1.

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer that has been on the rise in recent times, particularly among older individuals. Cornulin (CRNN) is increasingly recognized as an oncogene involved in developing various types of tumors. However, the precise contribution to cSCC remains unclear. Our study observed a significant increase in CRNN expression in cSCC samples compared to healthy skin. CRNN expression in the SCL-1 cell line derived from cSCC was reduced, leading to a halt in cell growth during the transition from the G1 phase to the S phase. This reduction inhibits cell division, promotes cell death, and decreases cell invasion and migration. CRNN overexpression has been found to enhance cell growth and prevent cells from undergoing natural cell death, and the cancer-promoting effects of CRNN are linked to AKT activation. Using a mouse xenograft model, we demonstrated that the inhibition of CRNN led to a decline in cSCC tumor growth in a living organism, providing evidence of CRNN's involvement in cSCC occurrence and development. This study establishes a foundation for evaluating the effectiveness of CRNN in treating cSCC, enabling further investigation in this area.

MiR-30c-5p inhibits esophageal squamous cell carcinoma progression by repressing the PI3K/AKT signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors, with high incidence and poor prognosis. Revealing mechanisms of ESCC progression and developing new therapeutic targets remains crucial. The aim of this study was to elucidate the molecular mechanism of miR-30c-5p in regulating the malignant progression of ESCC. TCGA, GEO, and other datasets were used to analyze the differential expression of miR-30c-5p in ESCC and adjacent tissues, and its impact on prognosis. Then the effects of miR-30c-5p on the proliferation, migration, and invasion of TE-1 and Eca9706 cells were investigated through proliferation experiments, transwell and wounding healing assays. The regulatory mechanism of miR-30c-5p on the PI3K/AKT signaling pathway and its interaction in cancer progression were investigated through Western blots, dual-luciferase reporter assay, and rescue experiments. miR-30c-5p was significantly downregulated in ESCC tissue and represented a poor prognosis. miR-30c-5p mimic significantly inhibited the proliferation, migration, and invasion ability of ESCC, while miR-30c-5p inhibitor significantly promoted tumor cell progression. Through bioinformatic analysis and experimental results, miR-30c-5p interacted directly with PIK3CA mRNA and inhibited subsequent signaling pathway activation. PIK3CA activator could eliminate the inhibitory effects of miR-30c-5p mimic on the progression of ESCC, while PIK3CA inhibitors could rescue the promoting effect of miR-30c-5p inhibitor group cells. In summary, we found that miR-30c-5p inhibited the proliferation, invasion and migration of ESCC by inhibiting PI3K/AKT signaling pathway for the first time, and this study is expected to provide a novel insight and potential therapeutic target for managing ESCC.

Association of Titin Polymorphisms with the Progression of Oral Squamous Cell Carcinoma and Its Clinicopathological Characteristics.

This study examined the correlation of titin (TTN) polymorphisms with the sensitivity of oral squamous cell cancer (OSCC) and clinical characteristics. Six TTN SNPs, including rs10497520, rs12463674, rs12465459, rs2042996, rs2244492, and rs2303838, were evaluated in 322 control groups and 606 patients with oral cancer. We then investigated whether the SNP genotypes rs10497520 had associations with clinical pathological categories. Our data showed that the TC + CC genotype of rs10497520 was associated with moderate/poor tumor cell differentiation. The carriers of TTN rs10497520 polymorphic variant "TC + CC" in OSCC patients with cigarette smoking were linked with poor tumor differentiation (p = 0.008). Our results suggest that the TTN SNP rs10497520 is a possible genetic marker for oral cancer patients in the cigarette-smoking population. The TTN rs10497520 polymorphisms may be essential biomarkers to predict the onset and prognosis of oral cancer disease.

Modulation of esophageal squamous cell carcinoma progression: the impact of CCR7 on JAK2/STAT3 signaling pathway

BackgroundExisting studies have already revealed the involvement of C–C chemokine receptor type 7 (CCR7) in diverse human cancers, including esophageal cell squamous carcinoma (ESCA). Our current study, aims to explore the relevant mechanisms implicated.MethodsESCA cell lines were collected for CCR7 expression quantification using western blot. Following the transfection, the viability, migration and invasion of ESCA cells were evaluated via cell counting kit-8 and Transwell assays. The specific molecular mechanisms underlying the effects of CCR7 in ESCA cells were explored via calculating the expressions of proteins related to metastasis and Janus kinase 2/signal transduction and transcription activation 3 (JAK2/STAT3) signaling pathway via western blot. The correlation between CCR7 and metastasis-related proteins was explored via Pearson’s correlation test.ResultsCCR7 was high-expressed in ESCA cells and CCR7 knockdown repressed the viability, migration and invasion of ESCA cells, concurrent with the increased expression of E-cadherin (E-cad, which was also known as CDH1 and lowly expressed in ESCA cells) and the decreased expressions of vimentin (Vim, which was highly expressed in ESCA cells) and matrix metalloproteinase-9 (MMP-9, which was also highly expressed in ESCA cells). Meanwhile, CCR7 was positively correlated with Vim and MMP-9 yet negatively correlated with E-cad in ESCA cells, which indicated that CCR7 has a role in promoting tumor progression in ESCA cells. Besides, the phosphorylation of STAT3 and JAK2 in ESCA cells was elevated, which was diminished following CCR7 knockdown.ConclusionThis study proves the modulation of CCR7 on ESCA in vitro, which was achieved via JAK2/STAT3 signaling pathway. Our discovery will provide new therapeutic basis and insights for ESCA.