Investigation of the SLC22A23 gene in laryngeal squamous cell carcinoma

Abstract 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

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

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

LKB1 mutations and their correlation with LKB1 and Rheb expression in bladder cancer

Although there are extensive studies on the genetics of bladder cancer, several questions remain unanswered. One of the pathways which are altered in bladder cancer is the mTOR signaling pathway. In the present study, we analyzed the expression of Rheb gene and genetic alterations in the LKB1 gene which are the key components of mTOR pathway. Nine exons of the LKB1 gene were analyzed by direct sequencing in 51 bladder cancer patients. To investigate the expression of Rheb and LKB1, real-time quantitative RT-PCR was performed in bladder tumor and normal bladder tissue samples. We did not observed a statistically significant difference in Rheb or LKB1 expression between the tumor and normal tissue samples. We detected a novel missense mutation creating stop codon in a high percent of the tumor samples. Five different single nucleotide substitutions were also observed in the introns. Our results indicate that LKB1 gene may play a role in the progression of bladder cancer. (c) 2012 Wiley Periodicals, Inc

DLEC1 is not silenced solely by promoter methylation in head and neck squamous cell carcinoma

Different types of genetic and epigenetic changes are associated with HNSCC. The molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive investigation. The Deleted in lung and esophageal cancer 1 (DLEC1) gene is frequently silenced by methylation in various kinds of cancer. However, there is no data in the literature investigating the DLEC1 gene in the HNSCC

Aryl butenoic acid derivatives as a new class of histone deacetylase inhibitors: synthesis, in vitro evaluation, and molecular docking studies

New aryl butenoic acid derivatives have been synthesized by combining hydroxy- or methoxy-substituted phenyl rings as the capping group, with a double bond in the short linker as well as metal binding groups, enoic ester, and salts bearing either methyl or morpholine. These compounds have been shown to possess promising histone deacetylase inhibition activities via in vitro fluorometric assay and molecular docking studies

Evaluation of brain MRI lesions in 381 girls with central precocious puberty

Central precocious puberty (CPP) in girls is a diagnosis increasingly made by the Pediatric Endocrinologists worldwide. Although it is most frequently of idiopathic origin, magnetic resonance imaging (MRI) of the brain is recommended to rule out organic lesions causing CPP. However, controversy exists regarding the age limits for routinely performing MRI in girls with CPP. Objective: To evaluate the outcome of brain MRI in girls diagnosed with CPP and its relationship with age and clinical and biochemical parameters. Method: A single-center, study of 381 girls with CPP who had brain imaging performed between 2008-2018. The results of imaging were categorised as Group 1:Normal, Group 2: incidental CNS lesions, Group 3: previously known CNS lesions Group 4: newly identified CNS lesions. Clinical and biochemical features of four groups were compared. Additionally, MRI lesion frequency was determined based on three age categories (8 years) Results: MRI findings were abnormal in 73 patients (19%). 18 girls (4.7%) had well known brain pathologies at the time of referral. In the remaining 363 girls with CPP, who had no CNS symptoms, MRI revealed CNS abnormalities in 55 girls. In 34 girls (8.9%) MRI findings were considered as incidental findings, which were not related to the early puberty. Another 21 girls (5.5%) had newly identified MRI abnormalities which were considered to be causally related to CPP. Among these, 19 lesions were non-neoplastic and included arachnoid cysts (6) pineal cysts (4) hydrocephaly (2) Chiari Type2 malformation (1) Dandy-Walker malformation(1) and others (5) not requiring surgical intervention during follow-up. There were only 2 tumoral lesions (0.5%) in the cohort (1 hamartoma and 1 glioma) and they required surgical intervention. These two cases were the youngest of the entire cohort (1.0 and 2.7 years of age respectively) and had the highest baseline LH and Estradiol levels. Otherwise, clinical and biochemical parameters were similar in 4 groups. Newly identified CNS lesions were detected throughout all ages including those above 8 years (Table). Conclusion: Although CNS lesions can be detected throughout all age categories in girls with CPP, only 5.5 % are causally related and most of them do not require intervention. CPP due to neoplastic lesions are detected in younger patients who also had a robust activation of pituitary-gonadal axis