Proliferation Of Oral Cancer Cells Research Articles

Elaeagnus angustifolia Plant Extract Induces Apoptosis via P53 and Signal Transducer and Activator of Transcription 3 Signaling Pathways in Triple-Negative Breast Cancer Cells.

Elaeagnus angustifolia (EA) is used as an alternative medicine in the Middle East to manage numerous human diseases. We recently reported that EA flower extract inhibits cell proliferation and invasion of human oral and HER2-positive breast cancer cells. Nevertheless, the outcome of EA extract on triple-negative breast cancer (TNBC) cells has not been explored yet. We herein investigate the effect of the aqueous EA extract (100 and 200 μl/ml) on two TNBC cell lines (MDA-MB-231 and MDA-MB-436) for 48 h and explore its underlying molecular pathways. Our data revealed that EA extract suppresses cell proliferation by approximately 50% and alters cell-cycle progression of these two cancer cell lines. Additionally, EA extract induces cell apoptosis by 40–50%, accompanied by the upregulation of pro-apoptotic markers (Bax and cleaved caspase-8) and downregulation of the anti-apoptotic marker, Bcl-2. Moreover, EA extract inhibits colony formation compared to their matched control. More significantly, the molecular pathway analysis of EA-treated cells revealed that EA extract enhances p53 expression, while inhibiting the expression of total and phosphorylated Signal Transducer and Activator Of Transcription 3 (STAT3) in both cell lines, suggesting p53 and STAT3 are the main key players behind the biological events provoked by the extract in TNBC cells. Our findings implicate that EA flower extract may possess an important potential as an anticancer drug against TNBC.

Combining structure-based and 3D QSAR pharmacophore models to discover diverse ligands against EGFR in oral cancer.

Background: Epidermal growth factor receptor-tyrosine kinase (EGFR-TK) is a well-known hallmark of oral and oropharyngeal cancers, as its overexpression leads to poor prognosis and malignancy. The activating EGFR mutations (particularly T790M and L858R double mutant) are a major challenge causing drug resistance, especially in the treatment of oral cancers. Methodology: This paper is an effort to exploit both structure-based and ligand-based pharmacophore modeling to discover EGFR-TK inhibitors, which showinhibition of proliferation of erlotinib-resistant FaDu and Cal27 oral cancer cells. Interestingly, the hit compound H2 also showed aneffect on the downstream glucose and lactate metabolism pathways. Conclusion: The results indicate the potential of H2 to be developed as anEGFR-based metabolic inhibitor for oral cancer treatment.

Novel Pathways and Mechanisms of Nicotine-Induced Oral Carcinogenesis.

Smokeless Tobacco (SLT) contains 9 times more nicotine than Smoked Tobacco (SMT). The carcinogenic effect of nicotine is intensified by converting nicotine-to-nicotine- derived Nitrosamines (NDNs). A review of the literature was conducted with a tailored search strategy to unravel the novel pathways and mechanisms of nicotine-induced oral carcinogenesis. Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release. Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance, and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers Ras/Raf-1/MEK1/ERK cascade, promoting anti-apoptosis and pro-proliferative effects. Furthermore, the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear localization of p-EGFR. Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of any carcinogenicity.

ML218 HCl Is More Efficient Than Capsaicin in Inhibiting Bacterial Antigen-Induced Cal 27 Oral Cancer Cell Proliferation.

The bacterial antigen, lipopolysaccharide (LPS) and disruptions in calcium channels are independently known to influence oral cancer progression. Previously, we found that bacterial antigens, LPS and lipoteichoic acid (LTA) act as confounders during the action of capsaicin on Cal 27 oral cancer proliferation. As calcium channel drugs may affect oral cancer cell proliferation, we investigated the effect of ML218 HCl, a T-type voltage-gated calcium channel blocker, on the proliferation of Cal 27 oral cancer cells. We hypothesized that ML218 HCl could effectively reduce LPS-induced oral cancer cell proliferation. LPS and LTA antigens were added to Cal 27 oral cancer cells either prior to and/or concurrently with ML218 HCl treatment, and the efficacy of the treatment was evaluated by measuring Cal 27 proliferation, cell death and apoptosis. ML218 HCl inhibited oral cancer cell proliferation, increased apoptosis and cell death, but their efficacy was significantly reduced in the presence of bacterial antigens. ML218 HCl proved more effective than capsaicin in reducing bacterial antigen-induced Cal 27 oral cancer cell proliferation. Our results also suggest an interplay of proliferation factors during the bacterial antigens and calcium channel drug interaction in Cal 27. Bacterial antigen reduction of drug efficacy should be considered for developing newer pharmacological agents or testing the efficacy of the existing oral cancer chemotherapeutic agents. Finally, voltage gated calcium channel drugs should be considered for future oral cancer research.

Tumor necrosis factor-α induced protein 8 (TNFAIP8/TIPE) family is differentially expressed in oral cancer and regulates tumorigenesis through Akt/mTOR/STAT3 signaling cascade

BackgroundHighest incidence of oral cancer is reported in India with reduced survival rate in the advanced stages due to lack of effective biomarkers. Therefore, it is essential to develop novel biomarkers for the better management of this disease. In the current study, TNFAIP8/TIPE protein family comprising of four proteins is explored for its role in oral cancer. MethodsIHC analysis of oral cancer TMA and Western blot analysis of tobacco treated oral cancer cells were performed to determine the differential expression of TIPE proteins in oral cancer. Further, CRISPR/Cas9-mediated gene editing was done to generate TIPE proteins' knockouts and MTT, colony formation, wound healing, cell cycle and Western blot analysis were performed to determine the effect of gene knockouts on various cancer hallmarks and the associated molecular targets of TIPE proteins. Results and discussionIHC results revealed that expression of TIPE, TIPE2 and TIPE3 were upregulated and TIPE1 was downregulated in oral cancer tissues compared to normal tissues. Similar results were observed upon treating oral cancer cells with tobacco carcinogens. Furthermore, knockout of TIPE or TIPE2 or TIPE3 significantly reduced the survival, proliferation, colony formation and migration of oral cancer cells whereas knockout of TIPE1 had an opposite effect. Further, TIPE, TIPE2 and TIPE3 knockout-mediated inhibition of proliferation was associated with inhibition of cell cycle progression at S or G2/M phases, and downregulation of proteins involved in cancer progression. We found that TIPE, TIPE1 and TIPE2 proteins regulate oral cancer progression through modulation of Akt/mTOR signaling cascade, whereas TIPE3 acts through an Akt-independent mTOR/STAT3 pathway. ConclusionCollectively, the TIPE proteins were proved to play significant roles in the progression of oral cancer thus warranting research and clinic attention for their therapeutic and prognostic values and raising the importance of specific targeting of TIPE proteins in cancer treatment.

Burmannic Acid Inhibits Proliferation and Induces Oxidative Stress Response of Oral Cancer Cells.

Burmannic acid (BURA) is a new apocarotenoid bioactive compound derived from Indonesian cinnamon; however, its anticancer effect has rarely been investigated in oral cancer cells. In this investigation, the consequences of the antiproliferation of oral cancer cells effected by BURA were evaluated. BURA selectively suppressed cell proliferation of oral cancer cells (Ca9-22 and CAL 27) but showed little cytotoxicity to normal oral cells (HGF-1). In terms of mechanism, BURA perturbed cell cycle distribution, upregulated mitochondrial superoxide, induced mitochondrial depolarization, triggered γH2AX and 8-hydroxy-2-deoxyguanosine DNA damage, and induced apoptosis and caspase 3/8/9 activation in oral cancer cells. Application of N-acetylcysteine confirmed oxidative stress as the critical factor in promoting antiproliferation, apoptosis, and DNA damage in oral cancer cells.

The Growth Factors and Cytokines of Dental Pulp Mesenchymal Stem Cell Secretome May Potentially Aid in Oral Cancer Proliferation.

Background: Growth factors and cytokines responsible for the regenerative potential of the dental pulp mesenchymal stem cell secretome (DPMSC-S) are implicated in oral carcinogenesis. The impact and effects of these secretory factors on cancer cells must be understood in order to ensure their safe application in cancer patients. Objective: We aimed to quantify the growth factors and cytokines in DPMSC-S and assess their effect on oral cancer cell proliferation. Materials and methods: DPMSCs were isolated from patients with healthy teeth (n = 5) that were indicated for extraction for orthodontic reasons. The cells were characterized using flow cytometry and conditioned medium (DPMSC-CM) was prepared. DPMSC-CM was subjected to a bead-based array to quantify the growth factors and cytokines that may affect oral carcinogenesis. The effect of DPMSC-CM (20%, 50%, 100%) on the proliferation of oral cancer cells (AW123516) was evaluated using a Ki-67-based assay at 48 h. AW13516 cultured in the standard growth medium acted as the control. Results: VEGF, HCF, Ang-2, TGF-α, EPO, SCF, FGF, and PDGF-BB were the growth factors with the highest levels in the DPMSC-CM. The highest measured pro-inflammatory cytokine was TNF-α, followed by CXCL8. The most prevalent anti-inflammatory cytokine in the DPMSC-CM was IL-10, followed by TGF-β1 and IL-4. Concentrations of 50% and 100% DPMSC-CM inhibited Ki-67 expression in AW13516, although the effect was non-significant. Moreover, 20% DPMSC-CM significantly increased Ki-67 expression compared to the control. Conclusions: The increased Ki-67 expression of oral cancer cells in response to 20% DPMSC-CM indicates the potential for cancer progression. Further research is needed to identify their effects on other carcinogenic properties, including apoptosis, stemness, migration, invasion, adhesion, and therapeutic resistance.

Eldecalcitol inhibits the progression of oral cancer by suppressing the expression of GPx-1.

This study aimed to investigate the role of eldecalcitol in the progression of oral squamous cell carcinoma and to explore the related mechanism. The effects of eldecalcitol on the proliferation, cell cycle, apoptosis, and migration of oral cancer cells (SCC-15 and CAL-27) were evaluated with cell counting kit-8, flow cytometry, quantitative real-time polymerase chain reaction, western blotting, and scratch assay. Mouse xenograft tumor model was established to further confirm the role of eldecalcitol in the progression of oral cancer. Immunohistochemistry, quantitative real-time polymerase chain reaction, and western blotting were used to detect glutathione peroxidase-1 expression in oral cancer tissue and cells treated with eldecalcitol. Eldecalcitol was found to inhibit the proliferation and migration of SCC-15 and CAL-27 cells significantly, block the cell cycle in the G0/G1 phase, and enhance the apoptosis. In addition, glutathione peroxidase-1 was downregulated by eldecalcitol and acted as an important medium of eldecalcitol in inhibiting the proliferation and migration of SCC-15 and CAL-27 cells, as well as promoting their apoptosis. Eldecalcitol may inhibit the progression of oral cancer by suppressing the expression of glutathione peroxidase-1, which may provide new insight into the application of eldecalcitol as a potential anti-cancer drug.

Bacterial Antigens Reduced the Inhibition Effect of Capsaicin on Cal 27 Oral Cancer Cell Proliferation.

Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells’ suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.

Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells.

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.

Circular RNA circFOXO3 regulates KDM2A by targeting miR-214 to promote tumor growth and metastasis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR‐214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor‐side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR‐214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR‐214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR‐214 to up‐regulate the expression of KDM2A, thus promotes tumor progression in OSCC.

CircVAPA promotes the proliferation, migration and invasion of oral cancer cells through the miR-132/HOXA7 axis.

ObjectiveTo study the relationship between the circular RNA vesicle-associated membrane protein-associated protein A (circVAPA) and the pathogenesis of oral squamous cell carcinoma.MethodsThe expression of circVAPA was detected by RT-qPCR. In vitro loss-of-function experiments were performed in Cal-27 cells. The malignant phenotype of cells was evaluated by cell counting kit-8, clone formation and transwell assays. Luciferase reporter assays were used to assess the circVAPA/miR-132/homeobox A (HOXA) regulatory axis.ResultscircVAPA expression was significantly increased in oral cancer tissues and cells. The overall survival and progression-free survival of patients with oral cancer who exhibited high circVAPA expression were significantly shorter compared with those with low expression. circVAPA expression was closely related to tumor size, TNM stage and distant metastasis. circVAPA knockdown reduced the proliferation, invasion and migration of Cal-27 cells. MiR-132 was identified as a target of circVAPA in Cal-27 cells. Cotransfection with si-circVAPA and miR-132 inhibitor reversed the inhibitory effect of circVAPA knockdown on cell malignant phenotypes. HOXA7 was further identified as a downstream target of miR-132.ConclusioncircVAPA is highly expressed in oral cancer, and its abnormal expression might affect the proliferation, invasion and migration of oral cancer cells by modulating the miR-132/HOXA7 signaling axis.

MCTS1 promotes invasion and metastasis of oral cancer by modifying the EMT process

BackgroundThe oncogene, malignant T-cell-amplified sequence 1 (MCTS1), has been found to be highly expressed in a variety of cancer cell lines. It has been shown to be involved in cell cycle progression and to confer a growth advantage for lymphomas and breast cancer. Nevertheless, the role of MCTS1 in contributing to the development of oral cancer remains elusive.MethodsWe analyzed the gene expression profiles of MCTS1 in normal oral keratinocytes and cancerous cells. Cellular proliferation, invasion, and migration experiments were performed to detect the effect of MCTS1 on the biological evolution of oral cancer. The in vitro results were verified by the in vivo lymphatic metastasis test. The underlying mechanism of MCTS1 in promoting oral cancer invasion and metastasis correlated with the epithelial-mesenchymal transition (EMT) process as revealed by western blotting.ResultsThe results showed that MCTS1 was aberrantly expressed in oral cancer cells. MCTS1 overexpression significantly promoted tumor cell growth, proliferation, migration, and invasion. MCTS1-mediated lymphatic metastasis was verified in vivo using an intraplantar tumor model. Biomarkers associated with EMT progression were positively or negatively regulated upon knockdown or overexpression of MCTS1, respectively.ConclusionsHigher MCTS1 expression in oral cancer may be connected with an unfavorable prognosis due to involvement of MCTS1. MCTS1 potentiates the growth and proliferation of oral cancer cells and subsequent metastasis by regulating cell cycle and modifying the EMT process.KeywordsOral cancer; oncogene; malignant T-cell-amplified sequence 1 (MCTS1); metastasis; invasion

Hsa‑miR‑5580‑3p inhibits oral cancer cell viability, proliferation and migration by suppressing LAMC2.

The present study aimed to explore whether and how microRNA-5580-3p (miR-5580-3p) affected oral cancer (OC) cell phenotypes via regulation of laminin subunit γ2 (LAMC2). Bioinformatics analysis was used to identify miR-5580-3p/LAMC2, a novel interactome that, to the best of our knowledge, has not been studied previously in OC. In the present study, the expression levels of miR-5580-3p and LAMC2 were detected by reverse transcription-quantitative PCR, while the protein expression levels of LAMC2 were identified using western blotting. To determine the effects of miR-5580-3p and LAMC2 in OC, a number of experiments, including Cell Counting Kit-8, 5-bromo-2′-deoxyuridine cell proliferation and wound healing migration assays, were performed using OC SCC-4 and Cal-27 cell lines. Additionally, luciferase reporter assays were employed to examine the interaction between miR-5580-3p and LAMC2 mRNA. The results demonstrated that miR-5580-3p expression was downregulated, while LAMC2 expression was upregulated in OC tissues and cell lines. In addition to the observation that miR-5580-3p promoted the malignant phenotypes of OC, it was also revealed that miR-5580-3p inhibited OC cell viability, proliferation and migration by suppressing LAMC2. Therefore, the present study suggested that miR-5580-3p and LAMC2 may be potential biomarkers and therapeutic targets for OC diagnosis and therapies in the future.

Tribulus terrestris fruit extract inhibits autophagic flux to diminish cell proliferation and metastatic characteristics of oral cancer cells

Elevated autophagy is highly associated with cancer development and progression. Fruit extracts of several plants inhibit activity of autophagy-related protease ATG4B and autophagy activity in colorectal cancer cells. However, the effects of these plant extracts in oral cancer cells remain unclear. In this study, we found that the extracted Tribulus terrestris fruit (TT-(fr)) and Xanthium strumarium fruit had inhibitory effects on autophagy inhibition in both SAS and TW2.6 oral cancer cells. Moreover, the fruit extracts had differential effects on cell proliferation of oral cancer cells. In addition, the fruit extracts hampered cell migration and invasion of oral cancer cells, particularly in TT-(fr) extracts. Our results indicated that TT-(fr) extracts consistently inhibited autophagic flux, cell growth and metastatic characteristics of oral cancer cells, suggesting TT-(fr) might contain function ingredient to suppress oral cancer cells.

Long non-coding RNA PTCSC3 inhibits human oral cancer cell proliferation by inducing apoptosis and autophagy.

IntroductionLong non-coding RNAs (lncRNAs) have gained increased attention due to the discovery of their roles in cancer-related processes. LncRNA PTCSC3 has been shown to have tumour-suppressive effects in thyroid cancer and glioblastoma. This study investigated the role of lncRNA PTSC3 in human oral cancer.Material and methodsCell viability was determined by MTT assay. The induction of apoptosis was confirmed by 4′,6-diamidino-2-phenylindole (DAPI) and Annexin V/PI assays. Ultrastructural analysis was performed by electron microscopy. Transwell assay was used to monitor the invasion of oral cancer cells.ResultsThe results revealed significant (p < 0.05) suppression of PTCSC3 expression in human oral cancer tissues and cell lines. The overexpression of PTCSC3 caused a significant (p < 0.05) decline in the proliferation of the human oral cancer cells via induction of apoptotic cell death which was accompanied by remarkable enhancement of Bax and suppression of Bcl-2. The electron microscopic analysis showed the development of autophagic vesicles in both the SCC-1 and SCC-9 cells indicative of autophagy. The western blotting analysis showed that PTCSC3 overexpression caused a remarkable increase in LC3B-I and Beclin 1 expression. PTCSC3 overexpression caused a significant (p < 0.05) decrease in invasion of the human SCC-1 and SCC-9 oral cancer cells. The invasion of the SCC-1 and SCC-9 cells was inhibited by 62% and 69% respectively.ConclusionsOverall, the evidence suggests that lncRNA PTCSC3 acts as a tumour suppressor in human oral cancer and suppresses oral cancer proliferation via induction of apoptosis and autophagy.

Combined Bacterial Antigen Lipopolysaccharide and Lipoteichoic Acid Increase Cal 27 Oral Cancer Cell Proliferation

Oral biofilms harbour gram-negative bacterial antigen lipopolysaccharide (LPS) involved in oral cancer progression and gram-positive bacterial surface-associated adhesive, lipoteichoic acid (LTA). Thus, we hypothesised that LPS and LTA together would increase the proliferation of cancer cells compared to stimulation by LPS alone. Oral cancer cell lines SCC4, SCC9, SCC25, Cal 27 and the normal oral cell line, OKF6, were studied. The bacterial antigen stimulation indices were determined using the MT Glo assay. Cell proliferation after bacterial antigen stimulation was validated by clonogenic assays. Phosphokinase array, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were employed to study proliferative and apoptotic pathways in bacterial antigen-stimulated cells. Bacterial antigens significantly stimulated Cal 27 (p ≤ 0.001) alone. SCC4 and SCC9 showed negligible stimulation with either antigen, while SCC25 results were comparable to OKF6. The combined antigen stimulation of Cal 27 led to a decrease in phosphorylated p53 and β-catenin and higher PI3K compared to LPS only stimulated cells (p ≤ 0.001). Combined bacterial antigen stimulation results in increased proliferation of Cal 27 cells due to lowering of tumor suppressor proteins and increased tumor proliferation-related proteins.

Overexpression of membranal SLC3A2 regulates the proliferation of oral squamous cancer cells and affects the prognosis of oral cancer patients.

Oral squamous cell carcinoma (OSCC) is the most common cancer in oral and maxillofacial tissue. This study aimed to investigate the expression of SLC3A2 in human OSCC tissues and its regulatory roles in OSCC. The expression of SLC3A2 in human OSCC tissues was assessed using immunohistochemistry. The proliferation, migration, and invasion of oral squamous cells were evaluated after knockdown of SLC3A2. The expression of SLC3A2 in OSCC was higher than that in normal oral epithelial cells. SLC3A2 had higher expression levels in OSCC tissues than that in adjacent normal tissues. Upregulation of SLC3A2 was associated with advanced stages and poor survival of OSCC patients. In vitro experiments showed that knocking down of SLC3A2 was associated with reduced migration, invasion, and proliferation, but increased apoptosis of OSCC cells. SLC3A2 exerted a harmful effect on OSCC patients by increasing migration, invasion and proliferation, and decreasing apoptosis.

NFAT5 promotes oral squamous cell carcinoma progression in a hyperosmotic environment

AbstractEpidermal growth factor receptor (EGFR) is highly expressed in several types of cancer cells including oral squamous cell carcinoma (OSCC). EGF/EGFR signaling is recognized as an important molecular target in cancer therapy. However, cancer cells often become tolerant to EGF/EGFR signaling-targeted therapies. In the tumor microenvironment, the tumor incites inflammation and the inflammation-derived cytokines make a considerable impact on cancer development. In addition, hyperosmolarity is also induced, but the role of osmotic stress in cancer development has not been fully understood. This study demonstrates molecular insights into hyperosmolarity effect on OSCC development and shows that NFAT5 transcription factor plays an important functional role in enhancing the oral cancer cell proliferation by inducing the EGFR translocation from the endoplasmic reticulum to the plasma membrane through increase the expression of DPAGT1, an essential enzyme for catalyzing the first committed step of N-linked protein glycosylation. These results suggest that hyperosmolarity-induced intra-nuclear translocation of NFAT5 essential for DPAGT1 activation and EGFR subcellular translocation responsible for OSCC tumor progression.This study demonstrates that NFAT5 promotes oral squamous cell carcinoma progression in the hyperosmotic environment through increased expression of DPAGT1, an essential enzyme for protein glycosylation, and altered EGFR subcellular localization from the cytoplasm to the plasma membrane in tumor cells.

LncRNA SNHG1 promotes the development of oral cavity cancer via regulating the miR-421/HMGB2 axis

Oral cancer (OC) is a common malignant tumor in oral surgery, which is prone to metastasis and the prognosis is not optimistic. Long-non-coding RNA (lncRNA) is a kind of endogenous transcripts with more than 200bp in length, lack of specific and complete open reading frame, and does not have the function of protein-coding. Studies have found that it can regulate gene expression at many levels, such as epigenetic level, transcriptional level and post-transcriptional level, thus affecting the occurrence and development of diseases. Recent studies have shown that the occurrence, development, of oral cancer, are associated with lncRNA. In this research, we found that lncRNA SNHG1 was up-regulated in oral cancer. Knockdown of lncRNA SNHG1 would inhibit the proliferation of oral cancer cells. Then we revealed a new mechanism that lncRNA SNHG1 regulated the growth of oral cancer via controlling the miR-421/HMGB2 axis, which provided new therapy for patients with oral cancer.