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Background/purpose: Accumulating evidence has suggested that treatment failure of cancer therapy can be attributed to cancer stem cells (CSCs). Among numerous regulators of cancer stemness, non-coding RNAs (ncRNAs) have gained significant attention recently. In this study, we examined the role of gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) in oral CSCs (OCSCs). Materials and methods: RNA Sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the expression of GAPLINC. Flow cytometry and sphere-forming assay were exploited to isolate OCSCs. Measurement of aldehyde dehydrogenase 1 (ALDH1) activity, CD44 expressing cells, and various phenotypic assays, such as self-renewal, migration, invasion, and colony-forming abilities, were conducted in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of GAPLINC. A luciferase reporter was also carried out to validate the direct interaction between GAPLINC and microRNA (miR)-331-3p. Results: Our results showed that GAPLINC was overexpressed in OCSCs from patient-derived and oral cancer cell lines. We demonstrated that silencing of GAPLINC in OCSCs downregulated various CSC hallmarks, such as ALDH1 activity, percentage of CD44-expressing cells, self-renewal capacity, and colony-forming ability. Moreover, our results revealed that the effect of GAPLINC on cancer stemness was mediated by direct repression of miR-331-3p. Conclusion: These data have potential clinical implications in that we unraveled the aberrant upregulation of GAPLINC and demonstrated that suppression of GAPLINC may reduce cancer stemness via sequestering miR-331-3p.
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Background/purpose: Emerging evidence has shown that various failures in cancer therapy, such as drug resistance, metastasis, and cancer relapse are attributed to cancer stem cells (CSCs). Also, growing attention has been paid to the regulation of non-coding RNAs in cancer stemness. Here, we aimed to investigate the contribution of LINC01296 in the modulation of oral CSCs. Materials and methods: The phenotypic assays including migration, invasion, and colony-forming abilities were carried out in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of LINC01296. In addition, the percentage of cells expressing stemness marker, ALDH1, and drug resistance marker, ABCG2, was examined as well as the self-renewal capacity after silencing of LINC01296. Moreover, a luciferase reporter was used to validate the direct interaction between LINC01296 and miR-143. Results: Our results showed that LINC01296 was significantly overexpressed in oral cancer tissues and positively correlated with stemness markers. The phenotypic and flow cytometry assays demonstrated that suppression of LINC01296 reduced the aggressiveness, cancer stemness features, and colony-forming and self-renewal abilities in oral CSCs. Furthermore, we demonstrated that LINC01296 may enhance cancer stemness features through suppression of the effect of miR-143. Conclusion: Silencing of LINC01296 may be a promising direction for oral cancer therapy by reducing cancer stemness via regulation of miR-143.
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Background/purpose: Oral cancer is one of the common cancers worldwide. Emerging evidence has indicated that microRNAs (non-coding RNA molecules of approximately 22 nucleotides in length) are implicated in the regulation of cancer stemness. However, the functional role of microRNA-509 (miR-509) in the characteristics of oral cancer stem cells (CSCs) has not been unraveled. Materials and methods: The expression level of miR-509 in ALDH1+ and sphere oral CSCs was examined by qRT-PCR. The aldehyde dehydrogenase 1 (ALDH1) activity and CD44 expression were assessed using flow cytometry. Self-renewal, transwell migration, and colony formation assays were conducted to measure the CSC phenotypes. Besides, a luciferase reporter assay was used to confirm the direct interaction between miR-509 and its target polo-like kinase 1 (plk1). Results: We showed the expression of miR-509 was downregulated in the CSCs derived from oral cancer cells (SAS), and upregulation of miR-509 diminished the several CSCs features, including ALDH1 activity, self-renewal capacity, CD44 expression, migration, and colony-forming abilities. Moreover, the result from the luciferase reporter assay validated the direct binding of miR-509 to plk1. Conclusion: Our results suggest that the miR-509/plk1 axis may mediate the cancer stemness in oral cancer, and targeting this axis may attenuate the progression of oral cancer.
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Background/purpose: Oral submucous fibrosis (OSF) has been regarded as a premalignant disorder of oral cancer, and myofibroblasts are the main cells that are responsible for pathological fibrosis. Hence, elucidation of the molecular mechanism underlying myofibroblast activation is important to treat OSF. MicroRNA-21 (miR-21) is a well-known fibrosis non-coding RNA, and its role in the development of OSF remains largely unclear. Materials and methods: Luciferase reporter assay was used to confirm the direct interaction between miR-21 and its target programmed cell death 4 (PDCD4). The expression level of PDCD4 in OSF was examined by qRT-PCR. Myofibroblast activities were assessed by collagen gel contraction and transwell migration assays. Results: Our result validated the direct binding of miR-21 to PDCD4. We showed the expression of PDCD4 was downregulated in OSF specimens and negatively correlated with miR-21. Our results suggested that overexpression of PDCD4 in fibrotic buccal mucosal fibroblasts (fBMFs) mitigated the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, we showed miR-21 contributed to myofibroblast activation of BMFs through repression of PDCD4. Conclusion: Our results suggest that the miR-21/PDCD4 axis mediates the myofibroblast activation of BMFs, and targeting this axis may exert an anti-fibrosis effect.
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Anterior immediate implant placement (IIP) has many biological and esthetic challenges, including inevitable soft and hard tissue loss after extraction. Previous literatures have discussed the facial bone architecture and defective socket classification. However, none of them discussed the depression of the cervical root area which can be seen frequently after IIP in type IIB and U-shaped defective sockets. In our limited experiences, we found that the labial interproximal bone edges of type IIB and U-shaped defect dominated the esthetic result after IIP. With more labial projection of the interproximal bone present, better esthetic result could be expected in the facial aspect. With adequate evaluation of this osseous scalloping before IIP, both patient and clinician could have a comprehensive understanding of the final esthetic result. This article also detailed the process of patient selection, diagnosis, surgical options, and executions required to achieve functional and esthetic success with IIP and provisionalization.
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BACKGROUND/PURPOSE: Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. METHODS: The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). RESULTS: We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. CONCLUSION: MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.
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microARN , Fibrose buccale sous-muqueuse , Régulation négative , Humains , microARN/génétique , microARN/métabolisme , Myofibroblastes/métabolisme , Fibrose buccale sous-muqueuse/génétique , Fibrose buccale sous-muqueuse/métabolisme , Tropomyosine/génétique , Tropomyosine/métabolisme , Tropomyosine/pharmacologieRÉSUMÉ
BACKGROUND/PURPOSE: Betel nut chewing is the major risk factor of oral submucous fibrosis (OSF). Various studies have sought to discover alternative strategies to alleviate oral fibrogenesis. In the present study, we aimed to evaluate the anti-fibrosis effect of paeonol, a phenolic component derived from Paeonia Suffruticosa. METHODS: The cytotoxicity of paeonol was tested using normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues. Collagen gel contraction, Transwell migration, invasion, and wound healing capacities were examined. Besides, the activation of TGF-ß/Smad2 signaling and expression levels of type I collagen, α-SMA, and long non-coding RNA HOTAIR were measured as well. RESULTS: Paeonol exerted a higher cytotoxic effect on fBMFs compared to normal BMFs. The arecoline-induced myofibroblast activities, including collagen gel contractility, cell motility, and wound healing ability were all suppressed by paeonol treatment. In addition, the activation of the TGF-ß/Smad2 pathway was inhibited along with a lower expression of α-SMA and type I collagen in paeonol-treated cells. Also, the administration of paeonol decreased the mRNA expression of HOTAIR in fBMFs. CONCLUSION: Our results indicate that paeonol may be a promising compound to attenuate the progression of oral fibrogenesis in OSF patients.
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Collagène de type I , Fibrose buccale sous-muqueuse , Acétophénones , Areca , Arécoline/pharmacologie , Transdifférenciation cellulaire/génétique , Cellules cultivées , Fibroblastes , Fibrose , Humains , Muqueuse de la bouche/anatomopathologie , Fibrose buccale sous-muqueuse/génétique , Facteur de croissance transformant bêtaRÉSUMÉ
BACKGROUND/PURPOSE: The habit of areca nut chewing has been regarded as an etiological factor of precancerous oral submucous fibrosis (OSF). In the present study, we aimed to evaluate the anti-fibrosis effect of honokiol, a polyphenolic component derived from Magnolia officinalis. METHODS: The cytotoxicity of honokiol was tested using normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues. Collagen gel contraction, Transwell migration, invasion, and wound healing capacities were examined. Besides, the expression of TGF-ß/Smad2 signaling as well as α-SMA and type I collagen were measured as well. RESULTS: Honokiol exerted higher cytotoxicity of fBMFs compared to normal cells. The arecoline-induced myofibroblast activities, including collagen gel contractility, cell motility and wound healing capacities were all suppressed by honokiol treatment. In addition, the expression of the TGF-ß/Smad2 pathway was downregulated along with a lower expression of α-SMA and type I collagen in honokiol-receiving cells. CONCLUSION: Our data suggest that honokiol may be a promising compound to alleviate the progression of oral fibrogenesis and prevent the transformation of OSF oral epithelium into cancer.
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Arécoline , Fibrose buccale sous-muqueuse , Areca , Arécoline/toxicité , Dérivés du biphényle , Transdifférenciation cellulaire , Fibroblastes , Humains , Lignanes , Muqueuse de la bouche , Fibrose buccale sous-muqueuse/induit chimiquement , Fibrose buccale sous-muqueuse/traitement médicamenteux , Protéine Smad2 , Facteurs de croissance transformantsRÉSUMÉ
BACKGROUND: No evidence is currently available to estimate the outcomes of intensity-modulated radiation therapy (IMRT) and surgery for patients with early oral cavity squamous cell carcinoma (E-OCSCC). METHODS: We recruited patients from the Taiwan Cancer Registry Database who had received a diagnosis of E-OCSCC. Propensity score matching was performed, and Cox proportional hazards model was used to analyze all-cause mortality. RESULTS: In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive IMRT, T2N0M0 compared with T1N0M0, and male patients compared with female patients were 0.303 (0.245, 0.375), 1.340 (1.077, 1.668), and 2.012 (1.432, 2.826), respectively. The aHRs (95% CIs) for age 61 to 70, 71 to 80, and â§81 years compared with <40 years were 2.984 (1.43, 4.225), 3.353 (2.578, 4.112), and 4.277 (4.104, 5.679), respectively. CONCLUSIONS: For patients with E-OCSCC, surgery may be considered the first option rather than definitive IMRT.
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Tumeurs de la tête et du cou , Radiothérapie conformationnelle avec modulation d'intensité , Sujet âgé , Études de cohortes , Femelle , Humains , Mâle , Adulte d'âge moyen , Stadification tumorale , Score de propension , Modèles des risques proportionnels , Études rétrospectives , Carcinome épidermoïde de la tête et du cou/radiothérapie , Carcinome épidermoïde de la tête et du cou/chirurgie , Taïwan/épidémiologieRÉSUMÉ
PURPOSE: Although patients aged >70 years are subject to early oral cavity squamous cell carcinoma (E-OCSCC), evidence is currently lacking regarding the probable outcomes of definitive radiotherapy (RT) compared to surgery in this population. METHODS: We recruited patients aged ≥70 years with a diagnosis of E-OCSCC from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze all-cause mortality of patients at different age intervals undergoing different treatments. RESULTS: The matching process yielded a final cohort of 604 patients in the definitive RT and surgery cohorts who were eligible for further analysis. These patients were classified as old (70-80 years) and very old (>80 years). In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR) (95% confidence interval [CI]) for surgery compared with definitive RT was 0.465 (0.354-0.610, P < 0.001). The aHR (95% CI) for age >80 years compared with age 70-80 years was 2.370 (1.720, 3.265, P < 0.001). The aHR (95% CI) for T2N0M0 compared with T1N0M0 was 1.752 (1.321-2.32, P < 0.001). The aHR (95% CI) for Charlson Comorbidity Index (CCI) ≥ 2 compared with CCI = 0 was 1.264 (1.137-1.738, P = 0.011). After stratified analysis, the aHRs for surgery compared with definitive RT were 0.484 (0.352-0.665, P < 0.001) and 0.411 (0.232-0.728, P = 0.002) among old and very old patients with E-OCSCC, respectively. CONCLUSIONS: Surgery may be more beneficial than definitive RT in selected elderly patients with E-OCSCC.
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Carcinome épidermoïde , Tumeurs de la tête et du cou , Tumeurs de la bouche , Sujet âgé , Sujet âgé de 80 ans ou plus , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/radiothérapie , Carcinome épidermoïde/chirurgie , Études de cohortes , Humains , Tumeurs de la bouche/anatomopathologie , Tumeurs de la bouche/radiothérapie , Tumeurs de la bouche/chirurgie , Stadification tumorale , Score de propension , Modèles des risques proportionnels , Études rétrospectives , Carcinome épidermoïde de la tête et du cou , Taïwan/épidémiologieRÉSUMÉ
Accumulating studies have indicated that long non-coding RNAs (lncRNAs) participate in the regulation of cancer stem cells (CSCs), which are crucial in tumor initiation, metastasis, relapse, and therapy resistance. In the current study, RT-PCR analysis was employed to evaluate the expression of LINC00963 in tumor tissues and oral CSCs. Stemness phenotypes and the expression of CSCs markers in oral cancer cells transfected with sh-LINC00963 were examined. Our results showed that the expression of the lncRNA LINC00963 was up-regulated in oral cancer tissues and CSCs. We found that the downregulation of LINC00963 inhibited CSC hallmarks, such as migration, invasion and colony formation capacity. Moreover, suppression of LINC00963 reduced the activity of stemness marker ALDH1, the percentage of self-renewal, chemoresistance and the expression of multidrug-resistance transporter ABCB5. Most importantly, we demonstrated that knockdown of LINC00963 decreased self-renewal, invasion and colony formation ability via ABCB5. Analysis of TCGA (the Cancer Genome Atlas) datasets suggested that the level of LINC00963 was positively correlated with the expression of the cancer stemness markers (Sox2 and CD44) and drug resistance markers (ABCG2 and ABCB5). Altogether, our results showed that suppression of LINC00963 may be beneficial to inhibit chemoresistance and cancer relapse in oral cancer patients.
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Oral submucous fibrosis (OSF) has been recognized as a precancerous disorder in the oral cavity. Great effort has been made to inhibit the malignant progression of OSF over the past decades, but the cure of this fibrosis disease has not been discovered. In the present study, we found that a long noncoding RNA, LINC00312, was upregulated in OSF tissues, and positively associated with several fibrosis factors, such as α-SMA, type I collagen, and fibronectin. As such, we sought to investigate the role of LINC00312 in OSF progression and identify its interacting factor that mediated oral fibrogenesis. Our results showed that the inhibition of LINC00312 downregulated the myofibroblast activities, including collagen gel contractility, transwell migration, and wound healing, as well as the gene expression of myofibroblast markers. We verified that YBX1 was a downstream factor of LINC00312 and revealed that the downregulation of YBX1 repressed the gene expression of α-SMA and p-Smad2 along with the reduced myofibroblast phenotypes. Most importantly, we demonstrated that the LINC00312-induced myofibroblast activities were reverted by the knockdown of YBX1, suggesting that the LINC00312-mediated myofibroblast transdifferentiation was through YBX1. Collectively, our findings revealed that the LINC00312/ YBX1 axis may serve as a target for the development of therapies against OSF.
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Régulation de l'expression des gènes , Myofibroblastes/métabolisme , Fibrose buccale sous-muqueuse/étiologie , Fibrose buccale sous-muqueuse/métabolisme , ARN long non codant/génétique , Protéine-1 de liaison à la boîte Y/génétique , Marqueurs biologiques , Prédisposition aux maladies , Technique d'immunofluorescence , Techniques de knock-down de gènes , Humains , Fibrose buccale sous-muqueuse/anatomopathologie , Protéine-1 de liaison à la boîte Y/métabolismeRÉSUMÉ
BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) is an oral precancerous disorder associated with the habit of areca nut chewing. MiR-10b has been shown to be upregulated in the oral cancer cells and induced by Twist. Our previous work has revealed that Twist participated in the pathogenesis of OSF and therefore we aimed to investigate whether Twist/miR-10b axis was involved in the activation of myofibroblast in the oral cavity. METHODS: The expression levels of miR-10b in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined. Besides, the expression of miR-10b was determined in fBMFs following knockdown of Twist or in BMFs after arecoline stimulation. Myofibroblast activities, including collagen gel contraction, migration and wound healing abilities, as well as the expression of α-SMA were measured in fBMFs treated with miR-10b inhibitor. Last, we investigated whether the effect of Twist overexpression could be reversed by suppression of miR-10b. RESULTS: MiR-10b expression was overexpressed in both OSF tissues and fBMFs. The silence of Twist resulted in the downregulation of miR-10b in fBMFs and arecoline treatment led to an increase of miR-10b in a dose-dependent manner. Inhibition of miR-10b ameliorated the activation of myofibroblasts and the expression of α-SMA. Moreover, we demonstrated that suppression of miR-10b hindered the increased collagen gel contraction caused by Twist overexpression. CONCLUSION: MiR-10b upregulation in OSF may be due to the stimulation of areca nut, leading to elevated myofibroblast activation. Our findings showed that the areca nut-induced expression of miR-10b was under the regulation of Twist and inhibition of miR-10b may provide a direction for treatment of OSF.
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microARN , Protéines nucléaires , Fibrose buccale sous-muqueuse , Protéine-1 apparentée à Twist , Areca , Arécoline/pharmacologie , Transdifférenciation cellulaire , Fibroblastes , Humains , microARN/génétique , Muqueuse de la bouche , Myofibroblastes , Protéines nucléaires/physiologie , Protéine-1 apparentée à Twist/physiologieRÉSUMÉ
Purpose: Although clinicians encounter patients aged ≥70 years with locally advanced oral cavity squamous cell carcinoma (LA-OCSCC), no evidence is available to facilitate decision making regarding treatment for this elderly population. Methods: We selected elderly (≥70 years) patients from the Taiwan Cancer Registry database who had received a diagnosis of LA-OCSCC. Propensity score matching was performed. Cox proportional hazards model curves were used to analyze all-cause mortality in patients in different age groups receiving different treatments. Results: The matching process yielded a final cohort of 976 patients in concurrent chemoradiotherapy (CCRT), non-treatment, radiotherapy (RT) alone, and surgery cohorts who were eligible for further analysis. After stratified analysis, the adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) derived for surgery, RT alone, and non-treatment compared with CCRT were 0.66 (0.52 to 0.83), 1.02 (0.81 to 1.28), and 1.52 (1.21 to 1.91), respectively, in patients aged 70 to 80 years. In the oldest patients (aged >80 years), multivariate analysis indicated that the results of surgery or RT alone were nonsignificant compared with those of CCRT. The aHR (95% CI) derived for the highest mortality was 1.81 (1.11 to 2.40) for non-treatment compared with CCRT. Conclusions: Surgery for elderly patients with LA-OCSCC is associated with a significant survival benefit, but the association is nonsignificant in the oldest elderly patients. No survival differences were observed between RT alone and CCRT in these elderly patients. Non-treatment should not be an option for these patients.
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BACKGROUND: To estimate easily assessed preoperative factors for predicting 90-day mortality in patients with a pancreatic head adenocarcinoma (PHA) receiving a pancreaticoduodenectomy. METHODS: We analyzed data from the Taiwan Cancer Registry Database of patients with a PHA who received a pancreaticoduodenectomy. Basic demographic characteristics, including gender and age, were categorized. The selection of preoperative comorbidities was based on the preoperative American Society of Anesthesiologists score and Charlson comorbidity index. RESULTS: We enrolled 8490 patients with a PHA who received a pancreaticoduodenectomy without distant metastasis. Currently, a pancreaticoduodenectomy for a PHA achieves an overall 90-day mortality rate of 8.39%. Univariate and multivariate Cox regression analyses indicated that an older age (65-74 and ≥75 years) and specific comorbidities (chronic obstructive pulmonary disease, chronic kidney disease, dementia, and sepsis) were significant independent prognostic factors for predicting 90-day mortality after a pancreaticoduodenectomy. After adjustment, the adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) of subjects with middle and high comorbidity scores for 90-day mortality in 65 to 74-year-old patients were 1.36 (1.05-1.75) and 2.25 (1.03-4.90), respectively, compared to subjects with low comorbidity scores. The aHRs (95% CIs) of subjects with middle and high comorbidity scores for 90-day mortality in ≥75-year-old patients were 1.35 (1.07-1.78) and 2.07 (1.19-3.62), respectively, compared to those with low comorbidity scores. CONCLUSIONS: Elderly patients with a PHA and moderate or high comorbidity scores have an increased risk of 90-day mortality after a pancreaticoduodenectomy.
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Adénocarcinome/mortalité , Tumeurs du pancréas/mortalité , Duodénopancréatectomie/mortalité , Adénocarcinome/épidémiologie , Adénocarcinome/anatomopathologie , Adénocarcinome/chirurgie , Facteurs âges , Sujet âgé , Comorbidité , Femelle , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Tumeurs du pancréas/épidémiologie , Tumeurs du pancréas/anatomopathologie , Tumeurs du pancréas/chirurgie , Pronostic , Facteurs de risque , Taux de survie , Taïwan/épidémiologieRÉSUMÉ
BACKGROUND/PURPOSE: Recurrent aphthous stomatitis (RAS) is common and associated with certain comorbidities. The aim of this study was to investigate the prevalence of selected comorbidities in patients with RAUs and to compare the risks of comorbidity between the two cohorts of patients with or without RAUs based on the Taiwanese National Health Insurance Research Database. METHODS: This case-control study included patients with recurrent aphthous stomatitis (the RAS cohort) and patients without recurrent aphthous stomatitis using 1:1 matching for year of index date, age, sex, monthly income, geographical location, and urbanization level (the non-RAS cohort). We calculated the prevalence of 31 medical comorbidities based on a modified version of the Elixhauser comorbidity index within 1 year before and after the index date. Conditional logistic regression was conducted to compare the risks of each comorbidity between the two cohorts. RESULTS: Compared with the non-RAS cohort, the RAS cohort had a significantly higher prevalence of 16 comorbidities, with 2% or higher prevalence difference for hyperlipidemia (2.9%), headaches (6.9%), liver diseases (2.8%), and peptic ulcers (5.4%). The adjusted odds ratios were >1.5 for headaches (1.92), migraines (1.62), hypothyroidism (1.50), rheumatoid arthritis (1.92), ankylosing spondylitis (1.94), systemic lupus erythematosus (1.82), liver diseases (1.51), peptic ulcers (1.69), hepatitis (1.62), depression (1.76), and psychoses (1.50). CONCLUSION: Patients with recurrent aphthous stomatitis were associated with increased risk of specific comorbidities. Physicians should screen for these comorbidities for early detection and treatment.
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Stomatite aphteuse/épidémiologie , Adolescent , Adulte , Répartition par âge , Sujet âgé , Études cas-témoins , Comorbidité , Bases de données factuelles , Femelle , Céphalée/épidémiologie , Humains , Hyperlipidémies/épidémiologie , Maladies du foie/épidémiologie , Modèles logistiques , Mâle , Troubles mentaux/épidémiologie , Adulte d'âge moyen , Prévalence , Facteurs de risque , Répartition par sexe , Taïwan/épidémiologie , Jeune adulteRÉSUMÉ
BACKGROUND: Oral submucous fibrosis (OSF) is a progressive scarring disease and has been considered as a premalignant condition of the oral cavity. However, the detailed molecular mechanisms underlying the pathogenesis of OSF are still unclear. METHOD: Here, we examined the expression of a novel long non-coding RNA LINC00974 in OSF and investigated its function role in myofibroblast transdifferentiation. Phenotypic analyses, including collagen gel contraction, migration, invasion and wound healing assays, were used to assess the myofibroblast activities following overexpression or inhibition of LINC00974. RESULTS: We found that the expression of LINC00974 in OSF tissues or myofibroblasts was aberrantly upregulated, and there was a positive correlation between LINC00974 and myofibroblast markers. Our results showed that inhibition of LINC00974 suppressed the myofibroblast activities, while overexpression of LINC00974 increased the activation. We demonstrated that the expression levels of α-SMA, α-1 type I collagen, fibronectin were downregulated in the LINC00974-inhibited myofibroblasts. Additionally, the TGF-ß secretion and phosphorylated Smad2 expression were also repressed in the LINC00974-inhibited myofibroblasts. We further demonstrated that silence of LINC00974 prevented the arecoline-induced myofibroblast activation, and LINC00974-increased myofibroblast activities were via TGF-ß pathway. CONCLUSION: Altogether, these findings suggested that arecoline-increased myofibroblast transdifferentiation was via LINC00974-mediated activation of TGF-ß signaling.
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Fibrose buccale sous-muqueuse/étiologie , Fibrose buccale sous-muqueuse/génétique , ARN long non codant/physiologie , Transduction du signal/génétique , Transduction du signal/physiologie , Protéines Smad/métabolisme , Facteur de croissance transformant bêta/métabolisme , Transdifférenciation cellulaire/génétique , Cellules cultivées , Expression des gènes , Humains , Myofibroblastes/anatomopathologie , Fibrose buccale sous-muqueuse/anatomopathologieRÉSUMÉ
Epithelial-mesenchymal transition (EMT) has been implicated in fibrogenesis and carcinogenesis; however, the exact role of EMT-inducer Slug in the progression of precancerous oral submucous fibrosis (OSF) has not been investigated. In the current study, we showed that the expression of Slug was upregulated in OSF tissues and associated with various myofibroblast markers. After silence of Slug in fibrotic buccal mucosal fibroblasts (fBMFs), the elevated myofibroblast activities and fibrosis markers were all downregulated. Our data revealed that arecoline, an areca nut alkaloid, increased the expression of Slug in normal BMFs, and inhibition of Slug successfully prevented the arecoline-induced myofibroblast activation. Additionally, overexpression of Slug in BMFs stimulated the activities of myofibroblasts, indicating that upregulation of Slug by arecoline contributes to the myofibroblast transdifferentiation. Most importantly, Slug was able to bind to the E-box of type I collagen, leading to increased expression of type I collagen. Altogether, this study demonstrated the abnormal elevation of Slug in OSF and its significance in arecoline-induced fibrogenesis. Moreover, downregulation of Slug could be a potential target for OSF remedy via suppression of myofibroblast activities and type I collagen.
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Transdifférenciation cellulaire , Muqueuse de la bouche/métabolisme , Myofibroblastes/métabolisme , Facteurs de transcription de la famille Snail/métabolisme , Arécoline/pharmacologie , Mouvement cellulaire/effets des médicaments et des substances chimiques , Transdifférenciation cellulaire/effets des médicaments et des substances chimiques , Collagène de type I/métabolisme , Transition épithélio-mésenchymateuse/effets des médicaments et des substances chimiques , Fibroblastes/effets des médicaments et des substances chimiques , Fibroblastes/métabolisme , Humains , Muqueuse de la bouche/effets des médicaments et des substances chimiques , Myofibroblastes/effets des médicaments et des substances chimiques , Fibrose buccale sous-muqueuse/traitement médicamenteux , Facteurs de transcription de la famille Snail/génétique , Régulation positive/effets des médicaments et des substances chimiquesRÉSUMÉ
Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide with poor prognosis. Numerous studies have attempted to explore alternative regimens aimed at reducing cancer stem cells (CSCs) without compromising the efficacy of conventional chemoradiotherapy. The present study sought to assess the effect of a natural compound honokiol on the reduction of elevated cancer stemness, metastatic capacity, and chemoresistance of oral carcinoma stem cells (OCSCs). Our results demonstrated that honokiol attenuated the cell survival and self-renewal of OCSCs in a dose-dependent manner. Moreover, honokiol downregulated the expression of 2 selective markers of OCSCs, ALDH1, and CD44, as well as the migration and invasion abilities, indicating its potential to suppress cancer stemness. We showed that honokiol reduced the secretion of IL-6 and phosphorylation of STAT3, and the honokiol-inhibited self-renewal, invasion and colony formation were reversed by administration of IL-6. Most importantly, our data demonstrated that honokiol was able to potentiate the effect of Cisplatin, leading to a lower proportion of OCSCs and the decreased cancer stemness features. Taken together, this study demonstrated the benefits of utilizing honokiol as an adjunct therapy for OSCC treatment.
Sujet(s)
Dérivés du biphényle/pharmacologie , Carcinome épidermoïde/anatomopathologie , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Interleukine-6/métabolisme , Lignanes/pharmacologie , Tumeurs de la bouche/anatomopathologie , Cellules souches tumorales/effets des médicaments et des substances chimiques , Facteur de transcription STAT-3/métabolisme , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Dérivés du biphényle/administration et posologie , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/métabolisme , Lignée cellulaire tumorale , Survie cellulaire/effets des médicaments et des substances chimiques , Cisplatine/administration et posologie , Cisplatine/pharmacologie , Régulation négative/effets des médicaments et des substances chimiques , Synergie des médicaments , Humains , Lignanes/administration et posologie , Tumeurs de la bouche/traitement médicamenteux , Tumeurs de la bouche/métabolisme , Cellules souches tumorales/métabolisme , Cellules souches tumorales/anatomopathologie , Transduction du signal/effets des médicaments et des substances chimiquesRÉSUMÉ
5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has been used in the treatment of various precancerous and malignant lesions. Our previous work has demonstrated that ALA-PDT possesses the potential to serve as an adjuvant therapy against head and neck cancer via eliminating the cancer stem cells (CSCs) property. This study aimed to further investigate the possible molecular mechanism underlying the effect of ALA-PDT. Our results revealed that ALA-PDT upregulated the expression of microRNA-145 (miR-145) in two oral cancer cell lines. Overexpression of miR-145 in oral CSCs further enhanced the treatment effect of ALA-PDT with lower self-renewal, invasion capacities and reduced CD44 expression, while inhibition of miR-145 exhibited the opposite phenomena. These findings suggest that the anti-CSCs effect of ALA-PDT is due to an elevation of miR-145.