Boosting Upconversion Efficiency in Optically Inert Shelled Structures with Electroactive Membrane through Electron Donation.

This study innovatively addresses challenges in enhancing upconversion efficiency in lanthanide-based nanoparticles (UCNPs) by exploiting Shewanella oneidensis MR-1, a microorganism capable of extracellular electron transfer. Electroactive membranes, rich in c-type cytochromes, are extracted from bacteria and integrated into membrane-integrated liposomes (MILs), encapsulating core-shelled UCNPs with an optically inactive shell, forming UCNP@MIL constructs. The electroactive membrane, tailored to donate electrons through the inert shell, independently boosts upconversion emission under near-infrared excitation (980 or 1550 nm), bypassing ligand-sensitized UCNPs. The optically inactive shell restricts energy migration, emphasizing electroactive membrane electron donation. Density functional theory calculations elucidate efficient electron transfer due to the electroactive membrane hemes' highest occupied molecular orbital being higher than the valence band maximum of the optically inactive shell, crucial for enhancing energy transfer to emitter ions. The introduction of a SiO2 insulator coating diminishes light enhancement, underscoring the importance of unimpeded electron transfer. Luminescence enhancement remains resilient to variations in emitter or sensitizing ions, highlighting the robustness of the electron transfer-induced phenomenon. However, altering the inert shell material diminishes enhancement, emphasizing the role of electron transfer. This methodology holds significant promise for diverse biological applications. UCNP@MIL offers an advantage in cellular uptake, which proves beneficial for cell imaging.

Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.

MicroRNA-204-5p is a tumor suppressor and potential therapeutic target in head and neck squamous cell carcinoma.

Elucidation of the molecular mechanisms governing aggressiveness of HNSCC may provide clinical therapeutic strategies for patients. In this study, a novel hub miR-204-5p functioning as tumor suppressor has been identified and explored in HNSCC. Methods: A novel hub miR-204-5p was identified based on miRNA microarray, bioinformatics analysis and validated in different HNSCC patient cohorts. The functional role of miR-204-5p and its downstream and upstream regulatory machinery were investigated by gain-of-function and loss-of-function assays in vitro and in vivo. Interactions among miR-204-5p and SNAI2/SUZ12/HDAC1/STAT3 complex were examined by a series of molecular biology experiments. Then, the clinical relevance of miR-204-5p and its targets were evaluated in HNSCC samples. HNSCC patient-derived xenograft (PDX) model was used to assess the therapeutic value of miR-204-5p. Results: We reveal that miR-204-5p as a tumor suppressor is commonly repressed in HNSCC, which can inhibit tumor growth, metastasis and stemness. Mechanically, miR-204-5p suppresses epithelial-mesenchymal transition (EMT) and STAT3 signaling by targeting SNAI2, SUZ12, HDAC1 and JAK2. Among these targets, we further showed that SNAI2, SUZ12, and HDAC1 form a repressive complex on CDH1 promoter to maintain EMT in HNSCC. In turn, the SNAI2/SUZ12/HDAC1 complex interacts with STAT3 on miR-204-5p-regulatory regions to suppress the transcription of miR-204-5p. Moreover, we also show that decrease of miR-204-5p indicates a poor prognosis in HNSCC patients and administration of agomiR-204-5p inhibits tumor growth and metastasis in HNSCC PDX models. Conclusion: miR-204-5p-SNAI2/SUZ12/HDAC1/STAT3 regulatory circuit has a critical role in maintaining aggressiveness of HNSCC, suggesting that miR-204-5p might serve as a promising therapeutic target for clinical intervention.

Validation of the International Tumor Budding Consensus Conference (2016) recommendations in oral tongue squamous cell carcinoma.

BACKGROUND: Tumor budding is a valuable prognostic marker in oral tongue squamous cell carcinoma (OTSCC) but lacks a standardized scoring system. The aim of this study was to evaluate the prognostic value of tumor budding for OTSCC patients based on the scoring system recommended by the International Tumor Budding Consensus Conference (ITBCC) 2016. METHODS: Tumor budding was scored as ITBCC recommended in 255 patients with OTSCC. Then, associations between tumor budding and clinicopathologic parameters were examined. Among them, 136 patients with follow-up data available were used to evaluate overall survival (OS) by the Kaplan-Meier method. Prognostic value of tumor budding was assessed by Cox regression analysis. The inter-observer and intra-observer agreement was calculated by the kappa statistic. RESULTS: Tumor budding score was associated with lymph node metastasis, differentiation, invasive pattern, lymphoid infiltrate, tumor relapse, invasive depth, and reduced OS in OTSCC patients. The Cox analysis showed high budding score was an independent prognostic factor in patients with all clinical stage and patients with clinical early-stage OTSCC. The high kappa values were achieved in intra-observer and inter-observer. CONCLUSIONS: International Tumor Budding Consensus Conference scoring system is a simple, reliable, and reproducible method to measure tumor budding in OTSCC, which should be included in the routine pathological report.

PLGA-based control release of Noggin blocks the premature fusion of cranial sutures caused by retinoic acid.

Craniosynostosis (CS), the premature and pathological fusion of cranial sutures, is a relatively common developmental disorder. Elucidation of the pathways involved and thus therapeutically targeting it would be promising for the prevention of CS. In the present study, we examined the role of BMP pathway in the all-trans retinoic acid (atRA)-induced CS model and tried to target the pathway in vivo via PLGA-based control release. As expected, the posterior frontal suture was found to fuse prematurely in the atRA subcutaneous injection mouse model. Further mechanism study revealed that atRA could repress the proliferation while promote the osteogenic differentiation of suture-derived mesenchymal cells (SMCs). Moreover, BMP signal pathway was found to be activated by atRA, as seen from increased expression of BMPR-2 and pSMAD1/5/9. Recombinant mouse Noggin blocked the atRA-induced enhancement of osteogenesis of SMCs in vitro. In vivo, PLGA microsphere encapsulated with Noggin significantly prevented the atRA-induced suture fusion. Collectively, these data support the hypothesis that BMP signaling is involved in retinoic acid-induced premature fusion of cranial sutures, while PLGA microsphere-based control release of Noggin emerges as a promising strategy for prevention of atRA-induced suture fusion.

Impact of tumor budding in head and neck squamous cell carcinoma: A meta-analysis.

Tumor budding (TB) has been suggested as an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). This meta-analysis evaluated the prognostic role of TB in HNSCC. We systematically reviewed the literatures of electronic databases and performed a meta-analysis to address the impact of TB on prognosis in HNSCC. Published data were extracted and organized. Then, pooled odds ratios for lymph node metastasis (LNM) and hazard ratios for survival were calculated by using the Mantel-Haenszel fixed effect model. The results showed that high TB was significantly associated with LNM and worse survival in patients with HNSCC. Moreover, high TB was also correlated with poor prognosis in patients with cT1-2N0 oral squamous cell carcinoma. TB is a promising prognostic factor associated with LNM and worse survival, which should be included in the routine pathological examination of HNSCC.

[Retracted] Long non­coding RNA MALAT1 interacts with miR­124 and modulates tongue cancer growth by targeting JAG1.

We wish to retract our research article entitled "Long non­coding RNA MALAT1 interacts with miR­124 and modulates tongue cancer growth by targeting JAG1" published in Oncology Reports 37 2087­2094, 2017. Following the publication of this article, it was drawn to our attention that this paper bore numerous similarites with an article published previously in the journal OncoTargets and Therapy. Although all the data reported in our study were original, we recognize that it was not appropriate that we should have modelled our paper on previously published articles as a template on which to base the writing of our paper. Therefore, we have agreed to follow the Editor's recommendation that this paper be retracted from the publication. All the named authors agree to this retraction. We sincerely apologize to the Editor and the readership of the Journal for our action, and regret any inconvenience this has caused. [the original article was published in the Oncology Reports 37: 2087­2094, 2017; DOI: 10.3892/or.2017.5445].

Activation of adrenergic receptor ß2 promotes tumor progression and epithelial mesenchymal transition in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is more aggressive than other cancers in the head and neck region because of its potential for metastasis. Recently, ß2­adrenergic receptor (ß2­AR) has been reported to be a potential promoter in various types of solid cancer. However, the role of ß2­AR and its effect on TSCC is not well documented. Histological staining, western blot analysis, migration and invasion assay were used. In this study, the expression of ß2­AR was increased in TSCC tissue compared with adjacent non­cancerous epithelium. Further analysis demonstrated that increased expression of ß2­AR was correlated with differentiation, lymph node metastasis and reduced overall survival rate in patients with TSCC. In vitro studies confirmed that activation of ß2­AR can promote epithelial mesenchymal transition in TSCC by initiating an interleukin­6/Stat3/Snail1 pathway. These results suggest that ß2­AR has an oncogenic role in TSCC and may be a potential therapeutic target in TSCC.

Determination of quantitative retention-activity relationships between pharmacokinetic parameters and biological effectiveness fingerprints of Salvia miltiorrhiza constituents using biopartitioning and microemulsion high-performance liquid chromatography.

In this study, we analyzed danshen (Salvia miltiorrhiza) constituents using biopartitioning and microemulsion high-performance liquid chromatography (MELC). The quantitative retention-activity relationships (QRARs) of the constituents were established to model their pharmacokinetic (PK) parameters and chromatographic retention data, and generate their biological effectiveness fingerprints. A high-performance liquid chromatography (HPLC) method was established to determine the abundance of the extracted danshen constituents, such as sodium danshensu, rosmarinic acid, salvianolic acid B, protocatechuic aldehyde, cryptotanshinone, and tanshinone IIA. And another HPLC protocol was established to determine the abundance of those constituents in rat plasma samples. An experimental model was built in Sprague Dawley (SD) rats, and calculated the corresponding PK parameterst with 3P97 software package. Thirty-five model drugs were selected to test the PK parameter prediction capacities of the various MELC systems and to optimize the chromatographic protocols. QRARs and generated PK fingerprints were established. The test included water/oil-soluble danshen constituents and the prediction capacity of the regression model was validated. The results showed that the model had good predictability.

Inhibition of periderm removal in all-trans retinoic acid-induced cleft palate in mice.

Cleft palate is a common craniofacial birth defect. The aim of the present study was to investigate the effect of excess all-trans retinoic acid (atRA) on periderm removal and the disappearance of basal medial edge epithelial (MEE) cells during palatogenesis, particularly during the stage prior to contact. atRA (200 mg/kg) was administered to C57BL/6N mice at embryonic day (E) 12.0 by gavage. Fetal palates were processed and analyzed by histology and electron microscopy. Single palate shelf peridermal cells were removed and cultured in the presence of atRA (3 µM) only or in the presence of or the caspase inhibitor, Z-VAD (100 µM) only, for 48 h. Once cultured, morphological changes were analyzed by histological staining and electron microscopy. A TUNEL assay was used to detect apoptotic neurons. Paired palatal shelves with periderm removal were cultured in the presence of atRA (3 µM) only or in the presence of Z-VAD (100 µM) only for 48 h and analyzed by hematoxylin and eosin staining. At E14.5, medial edge epithelium periderm was retained in the atRA-treated palates but had been shed prior to contact in the control groups. In addition, atRA was revealed to disrupt the cell cycle in the periderm by downregulating p21. Furthermore, atRA inhibited apoptosis in the periderm and basal MEE cells; however, atRA exhibited no effect on basement membrane degradation in single palatal organ culture. Additionally, once paired palates were cultured for 48 h, all of the groups in which the periderm had been removed exhibited confluence of the embryonic palatal mesenchyme. The present results suggest that periderm removal is inhibited in atRA-induced cleft palate in mice and that removal of the periderm contributes to EPM confluence in vitro.

Involvement of RBP4 in all­trans retinoic acid induced cleft palate.

The current study was designed to elucidate the mechanism of retinol binding protein 4 (RBP4) in cleft palate induced by all­trans retinoic acid (atRA). To establish a cleft palate model in C57BL/6J mice, pregnant mice were administered atRA (100 mg/kg) by gavage at the tenth embryonic stage (E10.0). Control groups were given the equivalent volume of corn oil. Pregnant mice were dissected at E12.5, E13.5 and E14.5 to obtain the embryonic palates. The expression levels of RBP4 in the embryonic palatal mesenchyme (EPM) were determined by immunohistochemistry, reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blotting. Human embryonic palatal mesenchymal cells were exposed to atRA to detect the variation in RBP4 induced by atRA in vitro. Small interfering RNA was used to suppress the expression of RBP4, and a plasmid overexpressing RBP4 was used to examine upregulated expression. The cell counting kit­8 assay was used to evaluate the effect of RBP4 on cell proliferation. The expression levels of p27 and cyclin D1 were determined by RT­qPCR and western blotting, while the expression levels of extracellular signal­related kinase (ERK) 1/2 and protein kinase B (AKT) were assessed by western blotting. At E14.5, RBP4 was strongly expressed in the EPM, while it was downregulated following atRA treatment, which induced cleft palate in vivo. In vitro experiments indicated that atRA suppressed the expression of RBP4 and altered the expression of p27 and cyclin D1 to cause growth inhibition. Knockdown of RBP4 resulted in decreased expression of cyclin D1 and increased p27, and suppressed proliferation. Overexpression of RBP4 reversed the inhibitory effect of atRA and promoted proliferation via the ERK1/2 and AKT signaling pathways. These results suggested that RBP4 was involved in cleft palate induced by atRA and it can be suppressed by atRA to cause growth inhibition in the embryonic palate.

MicroRNA-218 promotes cisplatin resistance in oral cancer via the PPP2R5A/Wnt signaling pathway.

Accumulating data suggest that microRNAs (miRNAs) play a pivotal role in the regulation of tumor cell sensitivity to chemotherapeutic agents. Although the roles of a few miRNAs have been identified in cisplatin resistance, little is known in regards to the concerted contribution of miRNA­mediated biological networks. In the present study, we demonstrated that microRNA-218 (miR-218) was significantly upregulated in cisplatin-resistant oral cancer cells. The results of cell viability and apoptosis assay showed that ectopic expression of miR-218 induced cell survival and resistance to cisplatin, whereas suppression of miR-218 caused apoptosis and enhanced sensitivity to cisplatin. Moreover, we identified PPP2R5A as a new direct target of miR-218 by using the dual luciferase reporter assay. Overexpression of miR-218 led to inhibition of PPP2R5A expression, whereas knockdown of miR-218 increased PPP2R5A levels. Introduction of PPP2R5A abrogated miR­218-mediated cell survival and drug resistance. Furthermore, suppression of miR-218 or PPP2R5A significantly promoted or reduced cisplatin-induced apoptosis, respectively. Finally, PPP2R5A overexpression or ß-catenin knockdown inhibited miR-218-mediated Wnt activation and partially restored cell sensitivity. Our data revealed a molecular link between miR-218 and PPP2R5A/Wnt signaling and implicates miR-218 as a potential target for oral cancer therapy.

Involvement of Notch2 in all­trans retinoic acid­induced inhibition of mouse embryonic palate mesenchymal cell proliferation.

Cleft palate is among the most common congenital disorders, and can be induced by exposure to all­trans retinoic acid (atRA) during mice and human embryogenesis. However, the mechanism underlying the implication of atRA in the development of cleft palate has yet to be elucidated. In the present study, atRA administered by gavage resulted in formation of a cleft palate in 99% of treated C57BL/6 mice. Notch2 was revealed to be upregulated in mouse embryonic palate mesenchymal (MEPM) cells in the atRA­treated group compared with untreated control mice between embryonic day (E)12.5 and E14.5. In addition, atRA was demonstrated to mediate Notch2 expression via the activation of RA receptors (RARs). Since Notch2 activation has previously been reported to inhibit the proliferation of MEPM cells, the expression levels of extracellular signal­regulated kinase (ERK), p21, cyclin D1 and Ki­67 were assessed in samples from atRA­treated and control mouse embryos between E12.5 and E14.5. It was demonstrated that Notch2 silencing partially reversed the atRA­induced inhibition of ERK phosphorylation in MEPM cells. In addition, the atRA­induced cyclin D1 downregulation and p21 upregulation were partially reversed following Notch2 silencing, whereas the atRA­induced inhibition of cellular proliferation was also attenuated. Furthermore, it was revealed that Notch2 expression was upregulated, whereas Ki­67 expression was downregulated following atRA exposure, as assessed using resin bead­released atRA in MEPM cells. The present findings suggested that during embryonic development, atRA may enhance the expression of Notch2, which may inhibit cellular proliferation, possibly through ERK signaling.

Interplay between ΔNp63 and miR-138-5p regulates growth, metastasis and stemness of oral squamous cell carcinoma.

TP63 acts as a master regulator in epithelia development and in the progression of various cancers, but its role in oral cancer pathogenesis remains unknown. This study aimed to explore the role of TP63 in the progression of oral squamous cell carcinoma (OSCC). This study shows that ΔNp63, the predominant isoform of TP63, is significantly upregulated in OSCC tissues and cell lines compared with their normal counterparts, and its expression is closely correlated with pathological differentiation, lymph node metastasis and clinical stage in patients with OSCC. The overexpression of ΔNp63 promotes growth, metastasis and stem-like properties in OSCC cells, and ΔNp63 depletion significantly represses OSCC cellular phenotypes in vitro and in vivo. The ΔNp63 isoform transcriptionally suppresses miR-138-5p expression; restoration of miR-138-5p expression partially abolishes the effect of upregulating ΔNp63. This study also demonstrates that miR-138-5p directly targets ΔNp63, resulting in crosstalk with ΔNp63. The correlation between ΔNp63 and miR-138-5p was further validated in OSCC tissues and was found to be significantly associated with the prognosis of patients with OSCC. Therefore, our data reveal that the interplay between ΔNp63 and miR-138-5p promotes OSCC progression by regulating cell growth, metastasis and stemness.

Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), was the earliest discovered to be correlated with cancer and contributes to the initiation and development of several types of tumors. Dysregulation of MALAT1 expression is frequently observed in many types of cancer such as gastric cancer, esophageal squamous cell carcinoma and glioma. To date, the role of MALAT1 and the underlying mechanisms in tongue cancer development remain unclear. In the present study, we studied the influence of MALAT1 on tongue cancer cell lines and clinical tongue cancer samples so as to detect its function and the underlying mechanism. In the present study, lncRNA-MALAT1 was specifically upregulated in tongue cancer cell lines and overexpression promoted tongue cancer cell growth by targeting miR-124. Knockdown of MALAT1 suppressed the growth and invasion of human tongue cancer cells and inhibited metastasis in vitro and in vivo. In addition, miR-124-dependent jagged1 (JAG1) regulation was required for MALAT1-induced tongue cancer cell growth. Our data revealed that MALAT1 inhibited tongue cancer cell growth and metastasis through miR-124-dependent JAG1 regulation. In conclusion, we revealed that MALAT1 may play an oncogenic role by increasing proliferation and metastasis of tongue cancer and is a potential therapeutic target in human tongue cancer.

Evidence of phenotypic stability after transduction of fluorescent proteins in two human tongue cancer cell lines.

OBJECTIVES: This study investigated the phenotypic stability and biological properties of two human tongue cancer cell lines after transduction of fluorescent proteins. DESIGN: The human tongue cancer cell lines UM1 and UM2 were cultured with GFP and RFP lentiviral particles stock for 72h. Cells with successful transduction of fluorescent proteins were selected in a medium containing G418 antibiotics for two weeks. The proliferation rates of parental and transduced cell lines were evaluated by their population doubling time (PDT). Transduction efficiency was assessed by fluorescence microscope and flow cytometry. The transduced cells in passage 1, 2, 10, 20 and 30 were collected to check the stability of fluorescent protein expression. Phenotypic stability of the transduced cells was detected by means of cell morphology, cell surface markers and cell function evaluating essay. RESULTS: The proliferation rates of the transduced cell lines showed no significant difference compared to their parental cells. Successful transduction with high efficiency (99% up) was demonstrated. High fluorescence expression on both transduced cells was detected until the thirtieth generation. UM1 and UM1-GFP displayed mesenchymal cell characteristics, while UM2 and UM2-RFP cell lines showed properties characteristic of epithelial. CONCLUSIONS: Two human tongue cancer cell lines of epithelial and mesenchymal phenotype respectively, have been successfully labelled with green and red fluorescent proteins. The fluorescence maintained a high expression rate over thirty generations without influencing the original morphological phenotype and cadherin expression.

All-Trans Retinoic Acid-Induced Craniofacial Malformation Model: A Prenatal and Postnatal Morphological Analysis.

OBJECTIVE: To characterize the prenatal and postnatal craniofacial bone development in mouse model of all-trans retinoic acid (ATRA) exposure at different ages by a quantitative and morphological analysis of skull morphology. METHODS: Pregnant mice were exposed to ATRA at embryonic day 10 (E10) and 13 (E13) by oral gavage. Skulls of mice embryos at E19.5 and adult mice at postnatal day 35 (P35) were collected for high-resolution microcomputed tomography (microCT) imaging scanning and section HE staining. Reconstruction and measurement of mouse skulls were performed for prenatal and postnatal analysis of the control and ATRA-exposed mice. RESULTS: Craniofacial malformations in mouse models caused by ATRA exposure were age dependent. ATRA exposure at E10 induced cleft palate in 81.8% of the fetuses, whereas the palatine bone of E13-exposed mice was intact. Inhibitions of maxilla and mandible development with craniofacial asymmetry induced were observed at E19.5 and P35. Compared with control and E13-exposed mice, the palatine bones of E10-exposed mice were not elevated and were smaller in dimension. Some E10-exposed mice exhibited other craniofacial abnormalities, including premature fusion of mandibular symphysis with a missing mandibular incisor and a smaller mandible. Severe deviated snouts and amorphous craniofacial suture were detected in E13-exposed mice at P35. CONCLUSION: These morphological variations in E10- and E13-exposed mice suggested that ATRA was teratogenic in craniofacial bone development in mice and the effect was age dependent.

Consideration of precision medicine and big data in oral cancer / 口腔疾病防治

@#With the development of computer science and biotechnology, medical data has been dramatically increased and demonstrated the properties of variety and complexity. Biological and clinical researchers now face increasingly large and complex data sets. In the era of big data, strategies of diagnosis and treatment of cancer are gradually changed from evidence-based medicine to precision medicine. The promise of the big data paradigm may affect patients with oral cancer by enabling personalized monitoring, diagnosis and treatment. In this article, we will review the advances of diagnosis and treatment modality in oral cancer based on big data platform, which is mainly focused on oral cancer screening, early detection, molecular classification, prediction of metastasis and chemosensitivity.

Decreased miR-320a promotes invasion and metastasis of tumor budding cells in tongue squamous cell carcinoma.

We aimed to determine the specific miRNA profile of tumor budding cells and investigate the potential role of miR-320a in invasion and metastasis of tongue squamous cell carcinoma (TSCC). We collected tumor budding cells and paired central tumor samples from five TSCC specimens with laser capture microdissection and examined the specimens using a miRNA microarray. The specific miRNA signature of tumor budding cells was identified. We found that miR-320a was dramatically decreased in tumor budding cells. Knockdown of miR-320a significantly enhanced migration and invasion of TSCC cell lines. Suz12 was shown to be a direct target of miR-320a. Similar results were also observed in nude mouse models. Multivariate analysis indicated that miR-320a was an independent prognostic factor. Kaplan-Meier analysis demonstrated that decreased miR-320a and high intensity of tumor budding were correlated with poor survival rate, especially in the subgroup with high-intensity tumor budding and low expression of miR-320a. We concluded that decreased expression of miR-320a could promote invasion and metastasis of tumor budding cells by targeting Suz12 in TSCC. A combination of tumor budding and miR-320a may serve as an index to identify an aggressive sub-population of TSCC cells with high metastatic potential.

Overexpression of ß-Catenin Induces Cisplatin Resistance in Oral Squamous Cell Carcinoma.

Abnormal expression of ß-catenin contributes to tumor development, progression, and metastasis in various cancers. However, little is known about the relationship between abnormal expression of ß-catenin and cisplatin chemotherapy in oral squamous cell carcinoma (OSCC). The present study aimed to investigate the effect of ß-catenin on OSCC cisplatin resistance and evaluated the drug susceptibility of stable cell lines with ß-catenin knockin and knockdown. In this study, we found that higher expression level of ß-catenin can be observed in CDDP-treated cell lines as compared with the control group. Furthermore, the expression levels of ß-catenin increased in both a concentration- and time-dependent manner with the cisplatin treatment. More importantly, the nuclear translocation of ß-catenin could also be observed by confocal microscope analysis. Stable cell lines with CTNNB1 knockin and knockdown were established to further investigate the potential role and mechanism of ß-catenin in the chemoresistance of OSCC in vitro and in vivo. Our findings indicated that overexpression of ß-catenin promoted cisplatin resistance in OSCC in vitro and in vivo. We confirmed that GSK-3ß, C-myc, Bcl-2, P-gp, and MRP-1 were involved in ß-catenin-mediated drug resistance. Our findings indicate that the Wnt/ß-catenin signaling pathway may play important roles in cisplatin resistance in OSCC.