Epigenetic Silencing of SOX15 Is Controlled by miRNAs rather than Methylation in Papillary Thyroid Cancer.

METHODS: In this study, qRT-PCR was used to investigate the expression levels of the SOX15 gene and of miR-182, miR-183, miR-375, and miR-96 in thyroid tumors and adjacent noncancerous tissues. We also investigated the methylation status of the SOX15 promoter by methylation-specific PCR in tumors and adjacent noncancerous tissues. RESULTS: We observed a statistically significant downregulation of SOX15 expression in tumors compared to noncancerous tissue samples. The methylation levels of tumors and matched noncancerous tissues were similar, but miR-182, miR-183, and miR-375 expression levels were elevated in tumor tissues compared to noncancerous tissue samples. CONCLUSIONS: Our results indicate that SOX15 gene expression is associated with the pathogenesis of papillary thyroid carcinoma (PTC), and the epigenetic control of the SOX15 gene is regulated by miRNAs rather than by promoter methylation.

No Tumor Suppressor Role for LKB1 in Prostate Cancer.

To elucidate the pathogenesis of prostate diseases, following in silico analysis, the LKB1 gene was selected for further investigation. The LKB1 gene has been associated with poor prognosis and is frequently mutated in different types of cancers. In this study, 50 benign prostatic hyperplasia (BPH) and 57 prostate cancer (PCa) tissues, including matched normal tissue for the patients, were analyzed by qRT-PCR and DNA sequencing for LKB1 expression and the mutation profile, respectively. Expression of LKB1 was increased in 60.7% of the PCa tissues compared with noncancerous tissue samples (p ≤ 0.001). However, LKB1 expression was lower when compared with normal tissues in BPH (p = 0.920). Four coding sequence alterations were detected in BPH. Three silent mutations were located in codons 9, 32, and 275 and a missense mutation was observed in codon 384. Six alterations were identified in the intronic regions of the LKB1 gene in both PCa and BPH. Five mutations were observed in both patient groups. A new alteration in intron 6 was observed in a patient with PCa. The LKB1 gene may be associated with benign transformations rather than the tumors in prostate pathogenesis when its expression and mutation status are considered. However, the mechanism of LKB1 in PCa needs further studies.

Silencing of Wwox Increases Nuclear Import of Dvl proteins in Head and Neck Cancer.

Background: Wnt signaling pathway is associated with a variety of human cancers, including HNSCC. Wnt proteins control cellular events such as proliferation, fate specification, polarity, and migration by transducing signals to the nucleus through several cytoplasmic relay proteins. Although activation of the Wnt/ß-catenin pathway is a frequent event in various cancers, there is limited knowledge on the contribution of this signaling mechanism in HNSCC. The Wwox tumor suppressor protein participates in the regulation of Wnt signaling by interacting with Dvl proteins. Methods: In this study, we used qRT-PCR and western blotting to examine the mRNA and protein levels of the Dvls in association with WWOX in HNSCC cell lines and tumor tissues. Results: We found that silencing of WWOX leads to increased nuclear localization of the Dvl proteins in cell lines. However, we detected an increase only in the nuclear localization of Dvl-1 in tumor tissues. Conclusions: Our results suggest that aberrant WWOX expression contributes to HNSCC through the Wnt signaling pathway. Decreased expression of WWOX may function in HNSCC progression by allowing the nuclear localization of Dvl proteins.

Analysis of the DOK1 gene in breast cancer.

Breast cancer, which is the most common type of cancer among women, is a heterogenous disease. It results from progressive accumulation of genetic and epigenetic alterations in different genes. The Dok1 protein has been identified as the major substrate of protein tyrosine kinases in hematopoietic cells. It is considered as a tumor suppressor due to the reports which describe its inhibitory effect on major oncogenic signaling pathways such as Mek/Erk/PI3k/Akt and Wnt/ß-catenin. In this study, we investigated the mutation frequency of the DOK1 gene in 118 breast tumors using Sanger sequencing and DOK1 mRNA expression level in 63 breast cancer samples using qRT-PCR methods. Although the mutation frequency was low DOK1 mRNA expression levels were significantly reduced (63.5%) in the tumors compared to adjacent non-cancerous tissue. We also correlated expression changes with clinicopathological characteristics. Low mRNA levels correlated with age (p = 0.01) and c-erbB-2 (p = 0.05). In most of the previous reports, down-regulation of DOK1 mRNA expression has been associated with promoter methylation. We identified four different coding sequence alterations in 5.1% (6/118) of the tumor samples. However, all of these alterations were located in the functional domains of the protein. Therefore, these mutations may affect the function and/or cellular localization of the protein and contribute to cancer progression by this way. In conclusion our data indicate that DOK1 acts as a tumor suppressor in breast cancer and association of Dok1 with the c-erbB-2 mediated mechanism of action in breast cancer needs to be investigated.

ZNF703 is an important player in head and neck cancer.

OBJECTIVES: Despite advances in treatment, head and neck squamous cell carcinoma (HNSCC) remains difficult to treat and the overall survival rate has only modestly improved over the past years. Therefore, there is a need to understand the molecular mechanism of HNSCC. Zinc finger protein 703 (ZNF703) is an oncogenic transcription factor, and ZNF703 gene expression is altered in many cancers as a result of chromosome 8p12 amplification. The purpose of this study was to investigate the expression pattern of ZNF703 in HNSCC in association with CCND1 expression and Akt phosphorylation. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: One hundred and five patients with HNSCC. METHODS: Fifty HNSCC tumour and non-cancerous tissue samples were investigated by qRT-PCR and Western blotting. RESULTS: ZNF703 gene expression was increased in 22.9% of tumour tissues compared with its normal counterparts. The results were correlated with clinicopathological features, copy number variation and survival data. CONCLUSION: ZNF703 over-expression is associated with copy number variation and this over-expression may activate PI3K/Akt signalling pathway in HNSCC.

Downregulation of TCEAL7 expression induces CCND1 expression in non-small cell lung cancer.

Transcription Elongation Factor A-like 7 (TCEAL7) was first reported as a candidate tumor suppressor gene because of its inactivation in ovarian cancer as a result of promoter methylation. Down-regulation of the TCEAL7 gene expression was also associated with other cancers such as endometrial, breast, brain, prostate, gastric cancers, glioblastoma and linked to tumor phenotypes and clinical outcomes. However, there is no report in the literature investigating the role of TCEAL7 in non-small cell lung cancer. Cyclin D1 is an important molecule in the transition from G1 to S phase of the cell cycle, and is frequently deregulated in cancers. Cylin D1 (CCND1) gene is amplified or overexpressed in a variety of tumors. In our previous study we reported that CCND1 over-expression was not associated with amplification in non-small cell lung cancer. Recently, it has been reported that TCEAL7 regulates CCND1 expression through myc-binding E-box sequences. The aim of this study was to investigate the expression of TCEAL7 gene in non-small cell lung cancer and to determine its effect on the CCND1 expression level. For this purpose, expression levels of TCEAL7 and CCND1 genes were investigated in 50 patients with non-small cell lung cancer by quantitative real time polymerase chain reaction (qRT-PCR). TCEAL7 was under-expressed (68%) in non-small cell lung cancer tumor tissues while CCND1 was over-expressed (42%). The TCEAL7 levels negatively correlated with increased CCND1 expression (p = 0.002).

Pediatric Stroke: A Single-Center Experience.

The aim of this study was to evaluate the clinical characteristics, risk factors, treatment, and outcomes of pediatric stroke cases. A total of 118 patients diagnosed with arterial ischemic stroke (AIS), hemorrhagic stroke, and sinovenous thrombosis (SVT) between January 2000 and December 2011 were included. Neonatal cases were excluded. Demographic and clinical findings were retrospectively examined from medical records. We identified 118 patients with stroke. The age of the patients ranged from 1 to 215 months (17.92 y), with a mean age of 5.19±5.25 years. AIS accounted for the majority of cases (n=69, 58.5%), and the major etiology was cardiac disease (17%). Hemorrhagic stroke accounted for 19.5% (n=23) of the cases, and late hemorrhagic disease of the newborn was the major etiology (43%, n=10). SVT accounted for 22% (n=26) of the cases, and the major etiology was otitis media-mastoiditis (27%, n=7). Hemiplegia and headache were the most frequent symptoms for AIS and SVT, respectively. Stroke is rare in children compared with adults; however, it is detected more frequently with better imaging techniques and increased awareness. We found that children with AIS presented more commonly with hemiplegia and children with SVT with headache and strabismus. We did not find an association between thrombophilia and stroke.

The investigation of hyaluronic acid and hyaluronidase-1 levels as tumour marker in larynx cancer.

OBJECTIVE: The purpose of this study was to investigate the hyaluronic acid (HA) and hyaluronidase-1 (HYAL-1) levels in laryngeal cancer patients. STUDY DESIGN: Prospective, controlled clinical trial. SETTING: University Medical Center. PARTICIPANTS: Fifty laryngeal squamous cell carcinoma patients and 50 volunteers who gave saliva samples investigated prospectively between 2016 and 2017. METHODS: Hyaluronidase-1 expression was measured by RT-PCR in normal and tumour tissue samples; hyaluronic acid values of saliva and tumour tissues were measured by ELISA method. RESULTS: HYAL-1 expression increased 2.5-fold in tumour tissues compared to normal tissues, and the difference was statistically significant (P < 0.001).Mean saliva HA levels were 103.93 ± 69.04 ng/mL and 177.29 ± 98.44 ng/mL in the patients and controls' saliva specimens, respectively. The difference was not statistically significant (P = 0.657). HA levels were higher in tumour tissue samples than saliva samples, but there was not statistically significant difference between saliva and tumour tissue HA levels. CONCLUSION: HYAL-1 expression in laryngeal squamous cell carcinomas is elevated compared to normal tissues of same patients. Targeting this gene and HA catabolism products may use treatment of larynx cancer in the future.

Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation.

Breast cancer is the most common malignant tumor in women worldwide. Breast tumors mostly exhibit aberrant gene expression and DNA hypermethylation patterns that predispose the disease. Understanding the genetic and epigenetic factors that contribute to breast cancer development is important to identify novel diagnostic and prognostic markers. SCARA5: Scavenger receptor class A, member 5; is a member of the scavenger receptor family located on chromosome 8p21 which is a frequently deleted region in human cancers. SCARA5 has been identified as a candidate tumor suppressor gene in various kinds of cancer. However, its role in breast cancer remains unclear. Therefore, in the present study SCARA5 expression levels in breast tumors and matched noncancerous tissue samples from 77 patients were analyzed by qRT-PCR and the expression levels were correlated with the methylation level of SCARA5 gene promoter. We found that SCARA5 expression was significantly decreased in tumors (92.2%) compared to non-cancerous tissue samples and this down-regulation was associated with hypermethylation of the promoter (p < 0.001). A significant correlation was also detected between SCARA5 expression and the histological grade of the breast tumors (p = 0.017). Taken together, our results indicate that SCARA5 may play an important role in tumorigenesis of breast cancer via promoter methylation.

Investigation of the SLC22A23 gene in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer of the head and neck. In order to identify differentially expressed genes which may have a role in LSCC carcinogenesis, we performed GeneFishing Assay. One of the differentially expressed genes was the SLC22A23 (solute carrier family 22, member 23) gene. SLC22A23 belongs to a family of organic ion transporters that are responsible for the absorption or excretion of many drugs, xenobiotics and endogenous compounds in a variety of tissues. SLC22A23 is expressed in a various tissues but no substrates or functions have been identified for it. Although the exact function is unknown, single nucleotide polymorphisms (SNPs) which are located in SLC22A23 gene were associated with inflammatory bowel disease (IBD), endometriosis-related infertility and the clearance of antipsychotic drugs. On the other hand SLC22A23 is identified as a prognostic gene to predict the recurrence of triple-negative breast cancer. METHODS: To understand the role of the SLC22A23 gene in laryngeal carcinogenesis, we investigated its mRNA expression level in laryngeal tumor tissue and adjacent non-cancerous tissue samples obtained from 83 patients by quantitative real-time PCR. To understand the association between SNPs in SLC22A23 and LSCC, selected genetic variations (rs4959235, rs6923667, rs9503518) were genotyped. RESULTS: We found that SLC22A23 expression was increased in 46 of 83 tumor tissues (55.4%) and was decreased in 30 of 83 (36.1%) tumor tissues compared to normal tissues. 77.2% of patients were homozygote for genotype rs9503518-AA and they most frequently had histological grade 2 and 3 tumors. We also found that rs9503518-AA genotype is associated with increased SLC22A23 expression. CONCLUSIONS: Our results indicate that SLC22A23 may play a role in the development of laryngeal cancer.

PRR4: A novel downregulated gene in laryngeal cancer.

Head and neck squamous cell carcinomas (HNSCC) are a diverse group of tumor types, including neoplasia of the paranasal sinuses, oral cavity, trachea, pharynx and larynx. Laryngeal cancer is the most common type of HNSCC. The proline-rich 4 (PRR4) protein is synthesized in the acinar cells of human lacrimal glands. Previous studies have demonstrated that PRR4 may function as an antimicrobial protein protecting the ocular surface and the oral cavity. In order to determine differentially expressed genes (DEGs) in laryngeal tumors, a GeneFishing Assay was performed; 27 DEGs were identified. The PRR4 gene expression level in laryngeal tissue samples obtained from 90 patients, and the saliva of 25 healthy smokers and 25 non-smokers, was investigated using reverse transcription-quantitative polymerase chain reaction. It was revealed that PRR4 gene expression was decreased in 65/90 tumor tissues (72.2%) compared with normal tissues. No significant difference was identified between the healthy smoker and the non-smoker groups in terms of PRR4 gene expression. The results of the present study indicated that the PRR4 gene may serve an important role in laryngeal carcinogenesis.

Familial Mediterranean fever in childhood: a single-center experience.

The aim of this study is to present demographic and clinical features, MEFV mutation variations, and treatment response of a large number of pediatric familial Mediterranean fever (FMF) patients from a single tertiary centre. Moreover, we aimed to investigate the current outcome of FMF, namely frequency of amyloidosis in children with FMF. We evaluated 708 FMF patients who were followed up in our clinic and who were under colchicine treatment for at least 6 months. The data were recorded from patient records and also verified by negotiations with patients and parents. The male/female proportion of the cohort was 1.05/1 (n = 362/346). Abdominal pain (89.5%, n = 634) was the most common manifestation of FMF episodes, followed by fever (88.8%, n = 629) and arthritis (40.7%, n = 288). However, arthritis in 23 (8%) of the 288 cases was not self-limited; and they subsequently diagnosed with juvenile idiopathic arthritis in addition to FMF. Homozygote or heterozygote M694V mutation was more frequent in patients with arthritis (63.2%) and chronic arthritis (69.6%) than the whole cohort (53.8%). Erythrocyte sedimentation rate and CRP level were in high levels even during attack-free period in 13.9% (n = 97/697) and 11% (n = 78/670) of the patients, respectively. Proteinuria was found in ten patients (1.4%). Amyloidosis was confirmed by renal biopsy in only two of these cases who were homozygous for M694V and compound heterozygous for M694V/M680I. 47 (6.6%) subjects were considered as colchicine resistant. Homozygote M694V mutation was the most frequent mutation in those resistant cases (63.8%, n = 30), followed by compound heterozygote mutation of M694V/M680I (6.3%, n = 3). Homozygous M694V mutation are still the most frequent mutation and associated with the most severe clinical picture and the worst outcome in Turkish children. M694V genotype seems to be more frequently associated with arthritis as well as with chronic arthritis than other genotypes. Recurrence of FMF episodes as well as amyloidosis could only be managed via strict compliance to colchicine treatment. Frequency of amyloidosis significantly decreased compared to the previous studies. A favorable outcome could be obtained with the anti IL-1 in colchicine-resistant FMF patients.

IL-1ß polymorphism in COPD patients in Turkish population.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterized by persistent airflow limitation and is associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Interleukin-1 beta (IL-1ß) is a major pro-inflammatory cytokine expressed by many cells such as macrophages, neutrophils and monocytes and functions in cellular activities such as proliferation, differentiation and apoptosis. Recent studies demonstrate controversial results about the relationship between IL-1ß and COPD. The aim of this study is to investigate the association between IL-1ß -511 (rs 16944) and +3954 (rs 1143634) gene polymorphisms and COPD in Turkish population. MATERIALS AND METHODS: A total of 152 subjects were recruited in the study and divided into three groups: 72 COPD patients, 41 healthy smokers and 39 never-smokers. PCR-RFLP method was used to determine the allele frequencies, genotype and haplotype distributions. RESULT: We did not find any significant difference between the gene polymorphisms and COPD by means of genotype frequencies, haplotype association, stage, gender or smoking status (p< 0.05). CONCLUSIONS: Our results do not show any evidence of association between COPD and IL-1ß -511 and +3954 gene polymorphisms in Turkish population.

The EMSY Gene Collaborates with CCND1 in Non-Small Cell Lung Carcinogenesis.

Background: Lung cancer is the leading cause of cancer deaths. The main risk factor is smoking but the risk is also associated with various genetic and epigenetic components in addition to environmental factors. Increases in the gene copy numbers due to chromosomal amplifications constitute a common mechanism for oncogene activation. A gene-dense region on chromosome 11q13 which harbors four core regions that are frequently amplified, has been associated with various types of cancer. The important cell cycle regulatory protein cyclin D1 (CCND1) is an essential driver of the first core region of the Chr11q13 amplicon. Deregulation of CCND1 has been associated with different kinds of human malignancies including lung cancer. The EMSY (c11orf30) gene has been proposed as the possible driver of the fourth core of the 11q13 amplicon and its amplification has been associated with breast and ovarian cancers. There is no report in the literature investigating the EMSY gene in lung cancer. Methods: In this study, expression levels of the EMSY and CCND1 genes were investigated in 85 patients with non small cell lung cancer by Real Time PCR. Results: Expression of the EMSY and CCND1 genes were increased in 56 (65.8%) and 50 (58.8%) of the patients, respectively. Both genes showed a higher expression in the tumors when compared to normal tissues. A strong correlation was present between the expression rates of both genes (p<0.001). Patients with adenocarcinoma had higher expression levels of both genes (p=0.02). Conclusion: We conclude that EMSY and CCND1 work in collaboration and contribute to the pathogenesis of lung cancer.

Does telomerase activity have an effect on infertility in patients with endometriosis?

OBJECTIVE: This study aimed to investigate the role of telomerase activity in the development of endometriosis-related infertility by evaluation of the serum telomerase in eutopic and ectopic endometrial tissue. STUDY DESIGN: Eutopic endometrium, cystic wall/ovarian cortex, and venous blood were assessed in forty-seven patients. The following groups of patients were identified: females with endometriosis requiring surgical intervention and healthy control females. Patients with histopathologically confirmed endometriosis were further subdivided in the infertile (n=14) and fertile (n=17) groups. Patients who underwent hysterectomy and oophorectomy for benign gynecological conditions were enrolled in the healthy control group (n=16). Telomerase activity was evaluated with three-group, endometriosis-based and fertility-based designs. Analyses were performed regardless the menstrual cycle phase (Phase G), in proliferative (Phase P) (n=22) and secretory phases (Phase S) (n=25). Telomeric Repeat Amplification Protocol PCR was applied for telomerase activity assessment. All statistical analyses were performed with STATA 14.2, GraphPad Prisma 7.01. RESULTS: In analyses of the eutopic endometrium, with three-group design, a significant difference was not found in Phase G and P (p=0.58 and p=0.33, respectively). However, a statistical difference was shown in Phase S (p=0.008). A significant difference was not established in Phase G, P and S of endometriosis-based design (p=0.35, p=1.0, p=0.13, respectively). No difference was detected in Phase G and P of fertility-based design (p=0.66 and p=0.14, respectively), whereas in secretory phase difference was approved (p=0,049). Telomerase activity was not established in ectopic endometrium and in serum assessment. CONCLUSIONS: Telomerase activity is useless as a biomarker in peripheric blood analysis. The absence of activity in cystic wall approves the high differentiation of endometriosis tissue, what is the possible reason of low malignancy risk. The high rate of telomerase activity in the eutopic endometrium of the infertile group may be considered as a cause of endometriosis-related infertility.

CT120: A New Potential Target for c-Myc in Head and Neck Cancers.

Background: CT120 is a universally expressed protein with seven transmembrane domains. It functions in cell proliferation, survival and apoptosis by activating Raf/MEK/ERK and PI3K/Akt signaling pathways. Evidence suggests that CT120 plays important roles in lung carcinogenesis and oncogenic pathway activation. c-Myc is an important transcription factor modulating cell progression, apoptosis and cellular transformation. Previous studies have shown that MYC gene is amplified in many types of cancer including head and neck squamous cell carcinoma (HNSCC). Myc can regulate expression of many genes by binding to E-boxes. The aim of this study was to investigate the relationship between c-Myc protein and CT120 gene. Methods: Tumor and normal tissue samples from 50 patients with HNSCC were investigated with chromatin immunoprecipitation assay (ChIP), Illumina MiSeq, bisulphite sequencing and qRT-PCR. Results: c-Myc binds to all E-boxes except E-box 5 on CT120 promoter. The CpG dinucleotides were found to be partially methylated in all tumor and normal tissue samples. Bisulphite sequencing showed a 10% down-regulation in the methylation levels of the tumor tissues. CT120 gene was hypomethylated and up-regulated in 56% of the tumor tissue samples. Expression of c-Myc was significantly higher in tumor tissues than in non-cancerous tissue samples. MYC was overexpressed in 68% of the tumor tissue samples compared to normal tissues. The mean MYC levels were 2.42-fold higher in the tumor tissue samples. In 48% of the tumor tissues, MYC and CT120A mRNA were up- or down-regulated simultaneously (p<0.001). Conclusion: We show that CT120 gene is a target of c-Myc and it contributes to cancer progression in HNSCC.

CHD5 is a potential tumor suppressor in non small cell lung cancer (NSCLC).

Lung cancer is one of the deadliest types of cancers and genetic and epigenetic alterations play major roles in its development. Chromodomain (CHD) protein family acts in chromatin organization, regulation of transcription and also genomic stability and cancer prevention. Although CHD5, a member of this family was shown to contribute to major cellular events and functions as a tumor suppressor gene in various types of cancer, it is not clear whether CHD5 plays a role in lung carcinogenesis. The aim of this study was to investigate the possible role of CHD5 in progression of non-small cell lung cancer (NSCLC). Expression levels of CHD5 gene in 59 tumor and corresponding non-cancerous lung tissue samples were analyzed by qRT-PCR and the methylation status of the promoter region was investigated by methylation specific PCR (MS-PCR). The Akt phosphorylation levels were investigated by Western Blot (WB). CHD5 was down-regulated in 17 (39.5%) and up-regulated in 24 (55.8%) of tumor specimens. Even though the promoter of CHD5 was hypermethylated in 8 patients, it was not found associated with CHD5 gene expression (p=0.08). Akt phosphorylation was increased in 14 (53.8%) and decreased in 12 (46.2%) of the samples but no significant association was found between p-Akt phosphorylation and CHD5 expression (p=0.67). We suggest that CHD5 may act as a tumor suppressor gene in NSCLC.

ZNF703 Overexpression may act as an oncogene in non-small cell lung cancer.

Despite therapeutic advances, lung cancer remains one of the most common causes of cancer-related deaths worldwide. The ZNF703 gene has been identified as the driver of the 8p11-12 region and its amplification or overexpression has been associated with several types of cancers. It has also been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway. The aim of our study was to investigate the role of the ZNF703 gene in association with Akt/mTOR activation in non-small cell lung cancer (NSCLC). Expression levels in tumors and matched noncancerous tissue samples from 47 patients were analyzed by qRT-PCR and the Akt phosphorylation levels were investigated by Western blotting. Our results show that ZNF703 is up-regulated in 63.4% of NSCLC tumor samples. Althogh the correlation did not reach a statistically significant level Akt phosphorylation was increased in tumor tissues expressing high levels of ZNF703. The role of the ZNF703 gene has not been investigated in NSCLC. Our data show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway.

Downregulation of Rab25 activates Akt1 in head and neck squamous cell carcinoma.

Several studies have suggested that Ras-associated binding 25 protein (Rab25) is involved in the pathogenesis of human cancer. Although it has been demonstrated that the development of head and neck squamous cell carcinoma (HNSCC) is the result of an accumulation of multiple sequential genetic and epigenetic alterations in key genes with important functions in cell growth and the cell cycle, recent studies have indicated that HNSCC is a complex and heterogenous disease. To the best of our knowledge, there is no data regarding the regulation of the Rab25 gene at the mRNA or protein level in HNSCC. Furthermore, available data on Rab25 expression in other types of cancer are conflicting. The aim of the present study was to investigate whether Rab25 is involved in the development and/or progression of HNSCC, and to analyze the mechanisms underlying its effects in this type of cancer. The expression of Rab25 mRNA in HNSCC tissues and adjacent non-tumor tissue samples was measured using reverse transcription-quantitative polymerase chain reaction, while the level of the Rab25, Akt1 and phosphorylated-Akt1 proteins was measured using western blotting. Expression of Rab25 mRNA and protein was downregulated in 69.1% and 56.1% of tumor tissue samples, respectively. This downregulation was associated with an increase in p-Akt1 expression, in the absence of a change in total Akt1 protein levels, in tumor tissues compared with normal tissues. The current findings suggest that Rab25 acts as a tumor suppressor in HNSCC.

CT120A Acts as an Oncogene in Head and Neck Squamous Cell Carcinoma.

Squamous cell carcinoma of the head and neck (HNSCC) is among the most frequent cancers worldwide. The etiology and pathogenesis of HNSCC are influenced by multiple genetic factors in addition to environmental and lifestyle-related factors. However, the mechanism underlying the HNSCC is still far from clear. The membrane associated gene CT120 was previously identified from chromosome 17p13.3 as a lung cancer-associated gene. Its function as an activator of the Erk and Akt signaling pathways in human lung cancer cell lines suggested that CT120 has an oncogenic function. However, there is no data in the literature on the role of CT120 in any other cancer type. Therefore, the aim of this study was to determine the expression rate and probable function of CT120 in HNSCC. Tumor tissues from 50 patients were analyzed by real-time quantitative RT-PCR to investigate the expression rate and by direct sequencing to differentiate the CT120A and CT120B variants. CT120 overexpression was observed in 58% of tumors compared to non-cancerous tissue samples and this up-regulation was directly associated with the upregulation of the CT120A variant and with the stage of the disease (p=0.001). Our results indicate that the CT120 gene may function in the development of HNSCC.