Abnormal Decrease of Macrophage ALKBH5 Expression Causes Abnormal Polarization and Inhibits Osteoblast Differentiation.

Peri-implant tissue inflammation is an inflammatory injury that occurs in the soft and hard tissues surrounding the implant and is the main cause of short- or long-term failure of implant prosthetic restorations, which is compounded by bone loss and bone destruction in the alveolar bone of diabetes patients with peri-implantitis. However, the mechanisms underlying the persistence of diabetic peri-implantitis, as well as the essential connections and key molecules that regulate its start and progression, remain unknown. In this study, we discovered that M1 macrophage polarization was abnormally enhanced in diabetic peri-implantitis and influenced the osteogenic differentiation of mesenchymal stem cells. RNA sequencing revealed that ALKBH5 expression was abnormally reduced in diabetic peri-implantitis. Further mechanism study showed that ALKBH5 and its mediated m6A can influence osteogenic differentiation, which in turn influences the persistence of diabetic peri-implantitis. Our findings present a new mechanism for the suppression of osteoblast development in diabetic peri-implantitis and a new treatment strategy to promote anabolism by inhibiting ALKBH5.

Measurement of buccolingual inclination of posterior teeth and the curve of Wilson in patients with different sagittal skeletal patterns using cone-beam computed tomography / 口腔疾病防治

Objective@# To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns.@*Results @#Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth.@*Conclusions@#The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma.

Background: YTH domain containing 1 (YTHDC1), an N6-methyladenosine (m6A) modification reading protein, plays a key role in regulating RNA translation and degradation. However, the role of YTHDC1 in head and neck squamous cell carcinoma (HNSCC) cancer stem cells remains largely unknown. This study is aimed at investigating the role of YTHDC1 in HNSCC and exploring its role in regulating cancer stem cells. Methods: RNA sequencing was used to detect differentially expressed genes (DEGs) between SCC9 spheres and SCC9 cells and to uncover molecular pathways and target molecules associated with CSCs. We detected YTHDC1 expression in The Cancer Genome Atlas (TCGA) database data and clinical samples. Subsequently, YTHDC1 gene suppression assays were performed in HNSCC cell lines to investigate the effect of YTHDC1 on tumor cell stemness maintenance, proliferation, and migration capacity. To further confirm the role of YTHDC1 in regulating cancer stem cells in HNSCC, we analyzed online HNSCC single-cell transcriptomic data to investigate YTHDC1 expression patterns at the single-cell level and the correlation of these levels with the expression of stem cell markers. Results: YTHDC1 expression levels were significantly upregulated in SCC9 spheres, and YTHDC1 was aberrantly expressed in HNSCC tumor tissues. The increased YTHDC1 expression was closely correlated with the clinical characteristics of HNSCC patients. YTHDC1 regulates the malignant phenotype of HNSCC in both in vivo and in vitro studies. Further single-cell transcriptomic data analysis revealed that YTHDC1 positively correlated with malignant epithelial cell stemness capacity at the single-cell level, and that YTHDC1 was involved in regulating stemness maintenance in HNSCC. Conclusions: These findings suggest that YTHDC1 may serve as a biomarker for stem maintenance and malignant progression in HNSCC, providing new insights into the treatment of cancer.

TAB2 Promotes the Biological Functions of Head and Neck Squamous Cell Carcinoma Cells via EMT and PI3K Pathway.

Background: Transforming growth factor ß 1-activated kinase 1 binding protein 2 (TAB2) mediates a variety of biological processes through activated nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. TAB2 has been reported to be upregulated in a variety of tumors. However, little is known about its potential role in oral squamous cell carcinoma (OSCC). Material and Methods. Patients' clinicopathological and transcription data were obtained from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry staining was used to determine TAB2 expression in OSCC tissues (IHC). The expression of TAB2 in OSCC cell lines was detected by western blotting. The CCK-8 test and flow cytometry assay were utilized to evaluate cell proliferation, apoptosis, and cell cycle in OSCC cell lines. Enrichment analysis and identification of predicted signaling pathways were performed by Gene Ontology and KEGG analysis. Finally, the expression of downstream signal molecules was performed using western blotting to validate the mechanism investigations. Results: TAB2 expression level was aberrantly upregulated in OSCC patients. TAB2 expression was shown to be inversely associated to prognosis. The phenotypic of OSCC cells was considerably impacted by TAB2. OSCC cells with deleted TAB2 exhibit decreased proliferation and increased apoptosis. Additionally, OSCC progression is aided by TAB2 overexpression. Further mechanism studies showed that TAB2 could regulate the progression of OSCC by mediating the upregulation of EMT and PI3K-AKT signaling pathways. Conclusion: This study sheds light on the carcinogenic role of TAB2 in OSCC and provides a potential therapeutic strategy.

KLF14 inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells by downregulating WNT3A.

KLF14 belongs to the Krüppel-like factor (KLF) family of transcription factors. The KLF family activate and/or repress transcription in a promoter- and cell-dependent manner by interacting with co-suppressors or co-activators. However, the function and mechanism of KLF14 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) is unknown. This study explores the impact and molecular mechanism of KLF14 in hMSC osteogenic differentiation in vitro. We found that KLF14 was highly expressed in hMSCs, and KLF14 expression gradually decreased after inducing osteogenic differentiation. Inhibiting KLF14 expression promoted osteogenic differentiation of hMSCs. We also found that KLF14 interacted with the WNT3A promoter. This interaction decreased expression of WNT3A and downstream osteogenesis-related target genes in the WNT signaling pathway, and resulted in cell cycle arrest. In conclusion, we describe a new mechanism for KLF14 in differentiation of hMSCs into osteoblasts and suggest a new target for clinical therapeutics related to human bone development.

The preventive effect of Cuscutae Semen polysaccharide on bone loss in the ovariectomized rat model.

The seed of Cuscutae Semen has been used as a functional food to prevent osteoporosis and aging, and improve sexual function in Traditional Chinese Medicine. However, there is a little report on its beneficial effects on osteoporosis. The purpose of our study was to explore whether Cuscutae Semen polysaccharide (CSP) could prevent osteoporosis induced by estrogen deficiency in the ovariectomized rat model. The preventive effect of CSP was assessed using the ovariectomized (OVX) rat model by treatment with vehicle or CSP for 12 weeks. Serum indexes related to osteogenesis were measured using ELISA kits. The underlying mechanism of action of CSP was evaluated by qRT-PCR. The findings showed that CSP exerted bone protective effects via the increase of bone mass, BMD, IGF, TGF-ß, osteocalcin, and osteoprotegerin, and the decrease of TRAP and CTX levels in estrogen deficiency-induced osteoporosis, which is mediated by up-regulating the expression levels of Osterix, BMP-2, Runx2, and Smad5 and down-regulating the expression levels of TRAP, NFATc1, c-Fos, and cathepsin K. These findings suggested that CSP exhibited the preventive effects in the estrogen deficiency-induced osteoporosis via promoting bone formation and inhibiting bone resorption. Therefore, CSP may be developed as a promising agent for the prevention of estrogen deficiency-induced osteoporosis.

Role of Noxa in proliferation, apoptosis, and autophagy in human adenoid cystic carcinoma.

BACKGROUND: Noxa, which is subset of the Bcl-2 family of proteins, was previously reported to have considerable therapeutic potential in diverse cancers. However, its expression and role in salivary gland adenoid cystic carcinoma (ACC) have not been well studied. This study aimed to elucidate the expression and role of Noxa in salivary gland ACC. MATERIALS AND METHODS: The expression levels of NOXA and its association with overall survival in salivary gland ACC were analyzed by quantitative real-time PCR. We next examined the effects of Noxa overexpression or inhibition on colony formation, proliferation, apoptosis, and autophagy of salivary gland ACC cells. Furthermore, promoter analysis was performed to identify the potential transcriptional activator of NOXA. RESULTS: NOXA was markedly down-regulated and significantly correlated with a more aggressive phenotype and poor overall survival of salivary gland ACC. Ectopic expression of Noxa suppressed the viability and growth of ACC cells, which involved the induction of apoptosis and autophagy. Moreover, the transcriptional activity of NOXA gene could be enhanced by p53. CONCLUSION: The findings of this study indicate that Noxa, activated transcriptionally by p53, suppress the progression of ACC, whereby it regulates proliferation, apoptosis, and autophagy.

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1.

BACKGROUND/AIMS: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. METHODS: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. RESULTS: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. CONCLUSION: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

Lnc-NTF3-5 promotes osteogenic differentiation of maxillary sinus membrane stem cells via sponging miR-93-3p.

BACKGROUND: The function and the mechanism of long non-coding RNAs (lncRNAs) on the osteogenic differentiation of maxillary sinus membrane stem cells (MSMSCs) remain largely unknown. MATERIALS AND METHODS: The expression of lnc-NTF3-5 and Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and Alkaline Phosphatase (ALP) was examined by quantitative real-time PCR (qRT-PCR) in MSMSCs during the process osteogenic differentiation. Then the function of lnc-NTF3-5 was evaluated by loss- and gain-of-function techniques, as well as qRT-PCR, western blot, and Alizarin Red staining. In addition, the microRNAs (miRNAs) sponge potential of lnc-NTF3-5 was assessed through RNA immunoprecipitation, dual luciferase reporter assay, and in vivo ectopic bone formation. RESULTS: Lnc-NTF3-5, RUNX2, OSX, and ALP increased alone with the differentiation. Inhibition of lnc-NTF3-5 decreased the expression of RUNX2, OSX, and ALP both at mRNA and protein levels. Alizarin red staining showed similar trend. In contrast, overexpression of lnc-NTF3-5 presented totally opposite effects. Besides, overexpression of lnc-NTF3-5 could decrease the expression of microRNA-93-3p (miR-93-3p). Enhance miR-93-3p could also inhibit the expression level of lnc-NTF3-5. RNA immunoprecipitation demonstrated that lnc-NTF3-5 is directly bound to miR-93-3p and dual luciferase reporter assay proved that miR-93-3p targets 3' UTR of RUNX2 to regulate its expression. Ultimately, in vivo bone formation study showed that lnc-NTF3-5 and miR-93-3p inhibitor co-transfection group displayed the strongest bone formation. CONCLUSIONS: The novel pathway lnc-NTF3-5/miR-93-3p/RUNX2 could regulate osteogenic differentiation of MSMSCs and might serve as a therapeutic target for bone regeneration in the posterior maxilla.

miR-27b-3p Suppressed Osteogenic Differentiation of Maxillary Sinus Membrane Stem Cells by Targeting Sp7.

OBJECTIVE: To explore the critical role and function of miRNAs in the regulation of development and physiology of maxillary sinus membrane stem cell (MSMSC) osteogenesis. METHODS: Microarray analysis was performed to screen the miRNAs expression profiles during the process of MSMSC osteogenic differentiation. Quantitative real-time polymerase chain reaction was applied to verify the miRNAs expression profiles. Gain- and loss-of-function experiments were used to demonstrate that miR-27b-3p inhibited MSMSC osteoblastic differentiation. Bioinformatic analysis was performed to predict the potential target of miR-27b-3p and then demonstrated by luciferase reporter assay and western blot. The negative regulation between miR-27b-3p and Sp7 was further confirmed using mimic and inhibitor of miR-27b-3p in vitro. Xenograft mice model was generated to confirm the relationship between miR-27b-3p and Sp7 using recombinant adenoviruses in vivo. RESULTS: MiR-27b-3p was downregulated during osteogenic differentiation of MSMSCs. The expression of Sp7, alkaline phosphatase, and osteocalcin decreased when transfected with miR-27b-3p-mimic in MSMSCs after osteogenic differentiation. MiR-27b-3p directly targeted Sp7 and inhibited the MSMSC osteogenesis in vivo. CONCLUSION: MiR-27b-3p suppressed the osteogenic differentiation of MSMSCs by directly inhibiting Sp7.

miR-1827 inhibits osteogenic differentiation by targeting IGF1 in MSMSCs.

We recently reported that maxillary sinus membrane stem cells (MSMSCs) have osteogenic potential. However, the biological mechanisms of bone formation remain unclear. In this study, we investigated the role and mechanisms of microRNAs (miRNAs) in the osteogenic differentiation of MSMSCs. The expression of miRNAs was determined in differentiated MSMSCs by comprehensive miRNA microarray analysis and quantitative RT-PCR (qRT-PCR). We selected miR-1827 for functional follow-up studies to explore its significance in MSMSCs. Here, miR-1827 was found to be up-regulated during osteogenic differentiation of MSMSCs. Over expression of miR-1827 inhibited osteogenic differentiation of MSMSCs in vitro, whereas the repression of miR-1827 greatly promoted cell differentiation. Further experiments confirmed that insulin-like growth factor 1 (IGF1) is a direct target of miR-1827. miR-1827 inhibited osteogenic differentiation partially via IGF1, which in turn is a positive regulator of osteogenic differentiation. Moreover, miR-1827 suppressed ectopic bone formation and silencing of miR-1827 led to increased bone formation in vivo. In summary, this study is the first to demonstrate that miR-1827 can regulate osteogenic differentiation. The increase in miR-1827 expression observed during osteogenesis is likely a negative feedback mechanism, thus offering a potential therapeutic target to address inadequate bone volume for dental implantation through inhibiting miR-1827.

Long Noncoding RNA Sponges miR-454 to Promote Osteogenic Differentiation in Maxillary Sinus Membrane Stem Cells.

OBJECTIVE: Although increasing evidence has shown that long noncoding RNAs (lncRNAs) play an important regulatory role in pluripotency and differentiation of mesenchymal stem cells, little is known about the role of lncRNA in maxillary sinus membrane stem cells (MSMSCs). The goal of this study was to investigate the expression profile and function of lncRNAs on osteogenic differentiation of MSMSCs. MATERIALS AND METHODS: By using lncRNA microarray, we identify a novel osteogenesis differentiation-related lncRNA of MSMSCs (lncRNA-MODR). The functional role of lncRNA-MODR in regulating osteogenesis was evaluated by quantitative real-time polymerase chain reaction, western blot, and alizarin red staining. Bioinformatic analyses of the predicted target genes (gene ontology, pathway, and network analysis) were applied for further study of lncRNA-MODR. RESULTS: We show that lncRNA-MODR is gradually upregulated during osteogenic differentiation. lncRNA-MODR overexpression upregulated, whereas lncRNA-MODR silencing decreased the expression of the osteogenic key marker, runt-related transcription factor 2 (RUNX2). In-depth analyses showed that lncRNA-MODR acts as a molecular sponge for microRNA-454 (miR-454) and that prevents RUNX2 from mi-454-mediated suppression. CONCLUSION: The lncRNAs act as a competing endogenous RNA to sequester microRNA-454 (miR-454), leading to heightened RUNX2 expression and thus promotes osteogenesis of MSMSCs.

miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/ß-Catenin Pathway in Tongue Squamous Cell Carcinoma.

MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/ß-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/ß-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/ß-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.

Investigation of multipotent postnatal stem cells from human maxillary sinus membrane.

Maxillary sinus membrane (MSM) elevation is a common surgical technique for increasing bone height in the posterior maxilla prior to dental implant placement. However, the biological nature of bone regeneration in MSM remains largely unidentified. In this study, MSM tissue was obtained from 16 individuals during orthognathic surgery and used to isolate MSM stem cells (MSMSCs) by single-colony selection and STRO-1 cell sorting. The cell characteristics in terms of colony-forming ability, cell surface antigens, multi-differentiation potential and in vivo implantation were all evaluated. It was found that MSMSCs were of mesenchymal origin and positive for mesenchymal stem cell (MSC) markers such as STRO-1, CD146, CD29 and CD44; furthermore, under defined culture conditions, MSMSCs were able to form mineral deposits and differentiate into adipocytes and chondrocytes. When transplanted into immunocompromised rodents, MSMSCs showed the capacity to generate bone-like tissue and, importantly, maintain their MSC characteristics after in vivo implantation. These findings provide cellular and molecular evidence that MSM contains stem cells that show functional potential in bone regeneration for dental implant.

Beclin1 inhibits proliferation, migration and invasion in tongue squamous cell carcinoma cell lines.

OBJECTIVES: The role of autophagy is still a controversy in cancer development. In our previous study, we confirmed that decrease of autophagy activity promotes malignant progression of tongue squamous cell carcinoma (TSCC). However, the role of autophagy-related protein, Beclin1, has not well been documented in TSCC. In this study, we aim to elucidate the role of beclin1 in TSCC progression and investigate its potential mechanisms. MATERIALS AND METHODS: TSCC cell lines, SCC9 and SCC15 were used to generate the stable cells with transfection lentivirus BECN1 and sh-BECN1. Then, Beclin1 expression was detected with qPCR and western blot. Moreover, the expressions of autophagy-related proteins and tumor metastasis associated proteins were examined by western blot and ELISA. For functional analysis, MTT assay were performed to evaluate the proliferation activity and transwell assay was used to assess the migration and invasion ability. Finally, TSCC xenograft models were established to confirm the effect of Beclin1 on TSCC in vivo. RESULTS: The results showed that BECN1 and sh-BECN1 virus transfection significantly increased or decreased the mRNA and protein expression of Beclin1 in the transfected TSCC cells. Meanwhile, we also observed that Beclin1 could enhance the expression levels of LC3-II, ATG4 and ATG5. Then, we revealed that overexpression of Beclin1 inhibited proliferation, migration and invasion while knockdown of Beclin1 promoted proliferation, migration and invasion in TSCC cells. Furthermore, we demonstrated that vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 were involved in Beclin1-mediated inhibition of migration and invasion. More importantly, our data also confirmed that Beclin1 inhibited TSCC xenograft growth in vivo. CONCLUSION: Taken together, the results indicate that autophagy regulating gene, Beclin1, may contribute to the malignant phenotypes of TSCC cells and can be a potential target for oral cancer gene therapy.

Decrease of autophagy activity promotes malignant progression of tongue squamous cell carcinoma.

BACKGROUND: Autophagy is a catabolic process involving the degradation of cells' own unnecessary, injured, or aged proteins and recycling of degraded products to maintain hemostasis. Recently, studies indicated that autophagy plays a crucial role in cancer development. However, the role of autophagy in tongue squamous cell carcinoma (TSCC) has not been well documented. This study aims to assess the expression of autophagy-related protein and investigate its effect on TSCC. MATERIALS AND METHODS: Archival 50 TSCC samples were enrolled. Immunohistochemistry were performed to examine the expression of Beclin1 and LC3. Statistical analyses were carried out to assess the associations among clinicopathologic parameters. In vitro, cells were treated with rapamycin or 3-MA. Then, qPCR, western blot and immunofluorescence were performed to detect the expression of Beclin1 and LC3. Transmission electron microscopy was utilized to identify autophagsomes. For functional analysis, cell proliferation and cell cycle were evaluated with MTT assay and flow cytometer, respectively. At last, cell migration and invasion potentials were assessed by wound healing assay and transwell assay. RESULTS: We confirmed that down-regulation of Beclin1 and LC3 is a frequent event in TSCC. Then, we demonstrated that decreased expression of Beclin1 was associated with T stage, clinical stage and differentiation. Furthermore, we showed that activation of autophagy by rapamycin suppressed proliferation, migration and invasion while inhibition of autophagy by 3-MA promoted proliferation, migration and invasion in TSCC cells. CONCLUSION: Taken together, these data suggest that autophagy plays a pivotal role in the progression of TSCC.