Impact of Alcohol Dehydrogenase 7 Polymorphism and Alcohol Consumption on Risk of Head and Neck Squamous Cell Carcinoma: A Korean Case-Control Study.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is closely associated with alcohol consumption and individual genetic susceptibility, such as single nucleotide polymorphism (SNP) of alcohol dehydrogenase (ADH). This study aimed to investigate the association of ADH7 SNPs with the risk of HNSCC. METHODS: We analyzed ADH7 rs1573496C>G, rs3737482T>C, rs1154460G>A, and rs284787T>C SNPs in 250 patients with HNSCC and 322 controls in the Korean populations. Genotyping was conducted using the TaqMan assay. Linkage disequilibrium and haplotypes were analyzed. RESULTS: The odds ratios (OR) and 95% confidence intervals (CI) of the CT and CC genotypes of ADH7 rs3737482T>C were 0.48 (0.29-0.78) and 0.69 (0.49-0.96), indicating a significantly decreased risk. In SNP of rs1154460G>A, the OR and 95% CI of the AA genotype was 1.63 (1.11-2.40), showing a significant increase in the risk. Furthermore, SNPs of ADH7 rs3737482T>C and ADH7 rs1154460G>A exhibit synergistic interactions with alcohol composition on the risk of HNSCC. None of the haplotypes were associated with the risk of HNSCC. CONCLUSIONS: ADH7 rs3737482T>C and rs1154460G>A SNPs are associated with the risk of development of HNSCC in Koreans. They could serve as molecular biological markers to screen high-risk groups for HNSCC.

Ultrasonographic Localization of Parotid Gland Tumor Relative to the Facial Nerve Using Stensen's Duct Criterion.

PURPOSE: During the preoperative evaluation of parotid gland tumors, one of the main concerns is to determine the location of the tumors in relation to the facial nerve. This study aims to assess the value of ultrasound for determining the location of parotid gland tumors in relation to the facial nerve using Stensen's duct. METHODS: This is a retrospective cross-sectional study at a single institute. The subjects who underwent preoperative ultrasound and parotidectomy for parotid gland tumors were included. The subjects with incomplete operative records or no reference standard for the location of parotid gland tumor were excluded. The primary predictor was ultrasound tumor location, which was defined as the location of parotid gland tumors determined by preoperative ultrasound as to whether the tumors were superficial or deep to the facial nerve. The operative records were used as the reference standard for the location of parotid gland tumors. The primary outcome was diagnostic performances of preoperative ultrasound in predicting the location of parotid gland tumors, which were calculated by comparing ultrasound tumor location to the reference standard. Covariates were sex, age, type of surgery, tumor size, and tumor histology. Data analysis involved descriptive and analytic statistics; P < .05 was considered statistically significant. RESULTS: One hundred and two of 140 eligible subjects met inclusion and exclusion criteria. There were 50 male and 52 female, with a mean age of 53.3 years. Ultrasound tumor location was classified as deep in 29 subjects, superficial in 50, and indeterminate in 23. The reference standard was deep in 32 subjects and superficial in 70. Indeterminate ultrasound tumor location results were grouped as either deep or superficial to make every possible cross table in which ultrasound tumor location results were presented as a dichotomy. The mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the ultrasound to predict the deep location of parotid tumors were 87.5, 82.1, 70.2, 93.6, and 83.8%, respectively. CONCLUSIONS: Stensen's duct on ultrasound can be a useful criterion to determine the location of parotid gland tumor relative to the facial nerve.

Transoral thyroidectomy implemented by a novice surgeon: Efforts for safe implementation.

Background: This study aimed to evaluate the feasibility, safety, and early surgical outcomes of transoral robotic and endoscopic thyroidectomy conducted by a novice surgeon. Methods: We analyzed 27 patients who underwent transoral thyroidectomy between December 2018 and November 2021. All the surgeries were performed by a novice surgeon without prior endoscopic or robotic surgery experience; the surgeon had experienced 12 cases of transcervical thyroidectomy before adopting transoral thyroidectomy. Results: Of the 27 cases, 1 was converted to the transcervical approach due to poor bleeding control. Four cases had transient recurrent laryngeal nerve palsy, and three had transient hypoparathyroidism. Most of the patients were very satisfied with the postoperative cosmetic outcome. Conclusions: Transoral robotic and endoscopic thyroidectomies are feasible for the novice surgeon, with reasonable results in the early adoption stage if preparations are according to the suggested framework. Level of Evidence: Level 4.

Depletion of NK6 Homeobox 3 (NKX6.3) causes gastric carcinogenesis through copy number alterations by inducing impairment of DNA replication and repair regulation.

Genomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1, and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells.

Application of the transoral endoscopic vestibular approach for a benign upper neck mass: A case report.

RATIONALE: Excision of a benign neck mass is traditionally performed via the transcervical approach. In order to avoid visible scars in the neck, various remote access surgical approaches have been developed. The aim of this report is to present the technique of a transoral endoscopic vestibular approach for treatment of a benign upper neck mass. PATIENT CONCERNS: A 47-year-old female with an anterior upper neck mass and throat discomfort visited our institution. DIAGNOSIS: The computed tomography (CT) scans and ultrasound (US) images demonstrated a benign-appearing mass on the anterior upper neck area. INTERVENTIONS: The benign upper neck mass was successfully removed via the transoral endoscopic vestibular approach, without any complication. OUTCOMES: The final pathologic report indicated that the lesion was an epidermal cyst. The cosmetic result was excellent. LESSONS: From this case study, we can learn to apply a transoral endoscopic vestibular approach for removal of a benign upper neck mass. Based on the outcomes, endoscopic removal of the benign upper neck mass via a transoral vestibular approach can be useful for patients who wish to hide any anterior neck scar.

Comparison of postoperative cosmesis in transaxillary, postauricular facelift, and conventional transcervical thyroidectomy.

BACKGROUND: The most important advantage of remote-access robotic and endoscopic thyroidectomies is believed to be the excellent postoperative cosmesis. The purpose of this study was to compare directly the postoperative cosmetic outcomes of robotic/endoscopic thyroidectomy via gasless transaxillary and postauricular facelift approaches with those of conventional thyroidectomy. METHODS: We prospectively studied 100 patients who underwent robotic/endoscopic thyroidectomy using a gasless unilateral axillary (GUA) approach (50 patients) or a postauricular facelift approach (50 patients), and 50 who underwent conventional transcervical thyroidectomy. Postoperative cosmetic satisfaction scores and scar consciousness scores were evaluated at 3 months and 1 year after surgery using questionnaires developed by us. Vancouver scar scales were evaluated at the same time. The cosmetic satisfaction score was defined as the sum of the two cosmetic satisfaction questions with a rating scale of 1-5 each. The scar consciousness score was defined as the sum of the four scar consciousness questions with a rating scale of 0-3 each. RESULTS: The cosmetic satisfaction and scar consciousness scores were significantly lower (corresponding to greater satisfaction) in the transaxillary and postauricular facelift groups than the conventional group at 3 months and 1 year postoperatively. They did not differ between the transaxillary and postauricular facelift groups. However, the Vancouver scar scale score of the conventional group was significantly lower than those of the transaxillary and postauricular facelift groups (P < 0.001 in both). CONCLUSION: Robotic/endoscopic thyroidectomy via transaxillary or postauricular facelift approaches results in better cosmesis than the conventional approach. However, scar healing itself is worse in the transaxillary and facelift approaches than the conventional approach.

Guidelines for the Surgical Management of Oral Cancer: Korean Society of Thyroid-Head and Neck Surgery.

Korean Society of Thyroid-Head and Neck Surgery appointed a Task Force to provide guidance on the implementation of a surgical treatment of oral cancer. MEDLINE databases were searched for articles on subjects related to "surgical management of oral cancer" published in English. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. The quality of evidence was rated with use RoBANS (Risk of Bias Assessment Tool for Nonrandomized Studies) and AMSTAR (A Measurement Tool to Assess the Methodological Quality of Systematic Reviews). Evidence-based recommendations for practice were ranked according to the American College of Physicians grading system. Additional directives are provided as expert opinions and Delphi questionnaire when insufficient evidence existed. The Committee developed 68 evidence-based recommendations in 34 categories intended to assist clinicians and patients and counselors, and health policy-makers. Proper surgical treatment selection for oral cancer, which is directed by patient- and subsite-specific factors, remains the greatest predictor of successful treatment outcomes. These guidelines are intended for use in conjunction with the individual patient's treatment goals.

Ultrasonographic Criteria to Define the Lower Limits of Neck Node Levels 2 and 3.

OBJECTIVE: To find ultrasonographic landmarks to define the lower limits of neck node levels 2 and 3. METHODS: Data were collected prospectively between February 2014 and January 2015. In total, 103 patients were recruited (50 men and 53 women), and the mean age was 50.9 years (range: 18-89). At the lower level of the hyoid, we classified ultrasonographic findings as hyoid type (HT)1 when the internal and external carotid arteries were visualized separately, HT2 when the internal and external carotid arteries joined together, and HT3 when the common carotid artery was visualized. At the lower border of the cricoid cartilage, we classified ultrasonographic findings as cricoid type (CT)1 when the omohyoid reached the medial half of the common carotid artery, CT2 when the omohyoid reached the lateral half of the common carotid artery, CT3 when the omohyoid reached the medial half of the internal jugular vein, and CT4 when the omohyoid reached the lateral half of the internal jugular vein. RESULTS: At the lower border of the hyoid, HT1 was most commonly observed in 59.2%, whereas HT2 and HT3 were observed in 31.3% and 9.7%, respectively. At the lower border of the cricoid cartilage, CT3 was most commonly observed in 52.9%, whereas CT2, CT4, and CT1 were observed in 20.4%, 14.1%, and 12.6%, respectively. CONCLUSION: HT1 and CT3 can be suggested ultrasonographic landmarks for the lower limits of levels 2 and 3, respectively. LEVEL OF EVIDENCE: 2. Laryngoscope, 129:2487-2490, 2019.

Comparison of outcomes between hemithyroidectomy alone and hemithyroidectomy with elective unilateral central neck dissection in patients with papillary thyroid microcarcinoma.

BACKGROUND: There have been arguments over the efficacy of elective unilateral central neck dissection (CND) in patients with papillary thyroid carcinoma (PTC) <1 cm who underwent hemithyroidectomy. This study was designed to investigate locoregional recurrence and postoperative complications related to elective unilateral CND for papillary thyroid microcarcinoma (PTMC). METHODS: Five hundred thirty-seven patients who underwent hemithyroidectomy, with or without CND for PTMC, were included. We compared locoregional recurrence and postoperative complication rates between 138 patients who underwent hemithyroidectomy only (CND group) and 399 patients who underwent hemithyroidectomy with elective unilateral CND (CND+ group). RESULTS: Recurrence was observed in 32 patients. Twenty-two patients with recurrence were in the CND+ group and 10 were in the CND- group. Recurrence rate was not significantly different between the 2 groups (P = .434). CONCLUSION: Concomitant unilateral elective CND did not enhance outcomes of hemithyroidectomy for the treatment of PTMC.

Ultrasound-Guided Core Needle Biopsy for Head and Neck Mass Lesions in Patients Undergoing Antiplatelet or Anticoagulation Therapy: A Preliminary Report.

OBJECTIVES: We compared the complications and diagnostic adequacy of ultrasound (US)-guided core needle biopsy (CNB) for head and neck mass lesions between patients who did and did not receive antiplatelet/anticoagulation therapy. METHODS: This study was designed as a prospective case study including 146 consecutive patients who underwent US-guided CNB for head and neck mass lesions. Of these, 32 patients were undergoing antiplatelet/anticoagulation therapy involving aspirin, clopidogrel, cilostazol, and warfarin. RESULTS: None of the patients had clinical bleeding/hematoma in either group. Subclinical bleeding/hematoma recognized only by a US examination was not significantly different between the groups (P = .229). No other complications were noticed. The rate of unsatisfactory sampling was also not different between the groups (P > .999). Furthermore, when patients receiving aspirin (n = 18) were reclassified into the no-antiplatelet/anticoagulation therapy group, there was still no significant difference in the incidences of complications compared with the patients receiving clopidogrel, cilostazol, or warfarin (n = 14). CONCLUSIONS: Our study suggests that US-guided CNB is safe and provides good diagnostic results without necessitating the discontinuation of antiplatelet/anticoagulation therapy in patients with head and neck mass lesions. However, as this was a preliminary study, the cohort was relatively small. Larger studies are needed to confirm our findings.

Role of TLRs in the production of chemical mediators in nasal polyp fibroblasts by fungi.

OBJECTIVE: Fibroblasts are major supporting cells in nasal mucosa and can induce inflammatory process with recruitment of inflammatory cells. Airborne fungi have been suggested as an etiologic factor of chronic rhinosinusitis (CRS). The aim of this study was to investigate the interaction between airborne fungi and pattern recognition receptors (PRRs) in nasal fibroblasts. METHODS: Primary nasal polyp fibroblasts were cultured with Alternaria and Aspergillus for 48h. To determine the production of chemical mediators interleukine-6 (IL-6), IL-8, granulocyte-macrophage colony stimulating factor (GM-CSF), eotaxin, and regulated on activation normal T expressed and secreted (RANTES) were measured with enzyme immunoassay methods. PRRs for toll-like receptors (TLRs) and protease-activated receptors (PARs) mRNA were determined with reverse transcription polymerase chain reaction (RT-PCR). To determine the role of PRRs, fibroblasts were treated with small interfering RNA (siRNA). RESULTS: IL-6 and IL-8 productions were significantly increased by 50 and 100µg/ml of Alternaria. However, GM-CSF, eotaxin, and RANTES productions did not change. Aspergillus did not influence the production of chemical mediators from nasal polyp fibroblasts. TLR2 and TLR5 mRNA expressions were significantly increased by fungi and these two TLRs were associated with the production of IL-6 and IL-8. CONCLUSION: Alternaria interacts as a pathogen-associated molecular pattern with the PRRs, such as TLR2 and TLR5, which induce the production of inflammatory chemical mediators from nasal polyp fibroblasts. Airborne fungi enhance the innate immune defense mechanism and may be associated with the pathogenesis of nasal inflammatory diseases.

HDAC6 sustains growth stimulation by prolonging the activation of EGF receptor through the inhibition of rabaptin-5-mediated early endosome fusion in gastric cancer.

The aberrant regulation of histone deacetylase 6 (HDAC6) contributes to malignant progression in various types of cancer, but the mechanism underlying gastric carcinogenesis remains unknown. Aberrant HDAC6 overexpression was observed in a subset of human gastric cancer cells. HDAC6 knockdown caused the significant inhibition of gastric cancer cell growth without affecting the transition of cell cycles or the processing of cell death. We demonstrate that an increase in epidermal growth factor receptor (EGFR) signaling through decreased EGFR degradation was mediated by HDAC6 in gastric carcinogenesis. These results establish a molecular mechanism responsible for oncogenic HDAC6, explaining how EGFR signaling induced by the growth factor is sustained during the malignant progression of gastric cancer.

Effects of fungi and eosinophils on mucin gene expression in rhinovirus-infected nasal epithelial cells.

PURPOSE: Fungi, rhinoviruses (RVs), and eosinophils are associated with upper respiratory diseases. We evaluated the effects of fungal stimulation and eosinophil co-culture on the expression of mucin genes in RV-infected nasal polyp epithelial cells. METHODS: Nasal polyp epithelial cells were obtained from chronic rhinosinusitis patients. Cultured epithelial cells were stimulated with Alternaria and Aspergillus with or without RV-16 infection. The epithelial cells were co-cultured with eosinophils for 16 h. MUC4, MUC5AC, MUC5B, and MUC8 mRNA expressions in the epithelial cells were quantified using real-time RT-PCR. To determine the underlying mechanism, nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and mitogen-activated protein kinase (MAPK) inhibitors were used to inhibit mucin gene expression. RESULTS: Fungi and RV-16 induced mucin gene expression in nasal polyp epithelial cells. However, there was no synergistic increase in mucin gene expression, with the exception of MUC4 mRNA expression stimulated by 25 µg/mL Aspergillus. When RV-16-infected epithelial cells were stimulated with fungi and then co-cultured with eosinophils, MUC4, MUC5B, and MUC8 mRNA expressions increased. Mucin gene expression was inhibited by NF-κB inhibitors. CONCLUSIONS: RV-16, airborne fungi, and eosinophils may exacerbate the inflammatory process in nasal mucosal diseases by enhancing mucin gene expression.

Characteristic molecular signatures of early exposure to volatile organic compounds in rat liver.

OBJECTIVE: Investigation on whether the characteristic molecular signatures can discriminate individual volatile organic compounds (VOCs) and provide predictive markers for the detection of VOC exposure. METHODS: Transcriptomic analysis of liver tissues was performed 48 h after the single oral administration of three VOCs doses at LD25 or LD5 values, to Sprague-Dawley. RESULTS: Combination analysis of different multi-classifications suggested that 145 genes predicted VOC exposure. Additionally, Gene Set Enrichment Analysis of genes deregulated by VOCs revealed that T cell prolymphatic leukemia signaling was inactivated in all VOCs. CONCLUSIONS: These molecular markers could be widely implemented to assess and predict environmental exposure to VOCs.

MiR-145 functions as a tumor suppressor by directly targeting histone deacetylase 2 in liver cancer.

Aberrant regulation of histone deacetylase 2 (HDAC2) plays a pivotal role in the development of hepatocellular carcinoma (HCC), but, the underlying mechanism leading to HDAC2 overexpression is not well understood. We performed microRNA (miRNA) profiling analysis in a subset of HCCs, and identified four down-regulated miRNAs that may target HDAC2 in HCC. Ectopic expression of miRNA mimics evidenced that miR-145 suppresses HDAC2 expression in HCC cells. This treatment repressed cancer cell growth and recapitulated HDAC2 knockdown effects on HCC cells. In conclusion, we suggest that loss or suppression of miR-145 may cause aberrant overexpression of HDAC2 and promote HCC tumorigenesis.

Utility of multiple sampling in reducing variation of salivary interleukin-8 and interleukin-1ß mRNA levels in healthy adults.

BACKGROUND: Salivary mRNA biomarkers can exhibit significant variation over time. The purpose of this study was to investigate the pattern and magnitude of variation of salivary mRNA biomarkers and to explore the effect of performing replicate assays and multiple sampling on the dispersion of salivary biomarkers. METHODS: Salivary interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) mRNAs, developed as biomarkers for oral cancer detection, were selected and measured from 15 healthy subjects at 4 different time points on the same day. RESULTS: Salivary IL-8 and IL-1ß mRNA levels fluctuated randomly over time without predictable rhythm and showed higher within-subject biological variation than analytical variation. The dispersion of salivary IL-8 and IL-1ß mRNAs was more effectively reduced by taking multiple saliva sample measurements than by performing replicative assays. CONCLUSION: Taking multiple saliva samples can effectively reduce variation of salivary IL-8 and IL-1ß mRNA levels in healthy adults.

Targeted inactivation of HDAC2 restores p16INK4a activity and exerts antitumor effects on human gastric cancer.

Aberrant regulation of histone deacetylase 2 (HDAC2) was reported for gastric cancers. However, responsive cancer genes in disease onset and progression are less understood. HDAC2 expression was studied by quantitative RT-PCR and Western blotting. The functional consequences of HDAC2 knockdown on cell-cycle regulation, programmed cell death, and gene target identification was investigated by flow cytometry, Western blotting, electron microscopy, anchorage-independent colony formation, and cell migration assay and by whole-genome microarray. Therapeutic efficacy of HDAC2 knockdown was determined in nude mice with small hairpin expressing human gastric cancer cells. Epigenetic regulation of p16(INK4a) was studied by methylation-specific PCR and chromatin-IP to evidence HDAC2 or acetylated-histone-H4 binding at gene specific promoter sequences. HDAC2 gene and protein expression was significantly upregulated in different histopathologic grades of human gastric cancers and cancer cell lines. HDAC2 inactivation significantly reduced cell motility, cell invasion, clonal expansion, and tumor growth. HDAC2 knockdown-induced G(1)-S cell cycle arrest and restored activity of p16(INK4a) and the proapoptotic factors. This treatment caused PARP cleavage and hypophosphorylation of the Rb-protein, repressed cyclinD1, CDK4, and Bcl-2 expression and induced autophagic phenotype, that is, LC3B-II conversion. Some gastric tumors and cancer cells displayed p16(INK4a) promoter hypermethylation but treatment with 5-aza-deoxycitidine restored activity. With others the methylation status was unchanged. Here, chromatin-IP evidenced HDAC2 binding. Nonetheless, expression of p16(INK4a) was restored by HDAC2 knockdown with notable histone-H4-acetylation, as determined by chromatin-IP. Thus, p16(INK4a) is regulated by HDAC2. HDAC2 is a bona fide target for novel molecular therapies in gastric cancers.

Characteristic molecular signature for the early detection and prediction of polycyclic aromatic hydrocarbons in rat liver.

Predictions of toxicity are central for the assessment of chemical toxicity, and the effects of environmental toxic compounds are still a major issue for predicting potential human health risks. Among the various environmental toxicants, polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutant, and many PAHs are known or suspected carcinogens. In the present study, to investigate whether characteristic expression profiles of PAHs exist in rat liver and whether a characteristic molecular signature can discriminate and predict among different PAHs at an early exposure time, we analyzed the genome-wide expression profiles of rat livers exposed to PAHs [benzo[a]anthracene (BA), benzo[a]pyrene (BP), phenanthrene (PA) and naphthalene (NT)]. At early time-point PAH exposure, large-scale gene expression analysis resulted in characteristic molecular signatures for each PAH, and supervised analysis identified 1183 outlier genes as a distinct molecular signature discerning PAHs from the normal control group. We identified 158 outlier genes as early predictive and surrogate markers for predicting each tested PAH by combination of two different multi-classification algorithms with 100% accuracy through a leave-one out cross-validation method. In conclusion, the characteristic gene expression signatures from a rat model system could be used as predictable and discernible gene-based biomarkers for the detection and prediction of PAHs, and these molecular markers may provide insights into the underlying mechanisms for genotoxicity of exposure to PAHs from environmental aspect.

Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b.

UNLABELLED: Sirtuins are nicotinamide adenine dinucleotide oxidized form (NAD(+) )-dependent deacetylases and function in cellular metabolism, stress resistance, and aging. For sirtuin7 (SIRT7), a role in ribosomal gene transcription is proposed, but its function in cancer has been unclear. In this study we show that SIRT7 expression was up-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients. SIRT7 knockdown influenced the cell cycle and caused a significant increase of liver cancer cells to remain in the G1 /S phase and to suppress growth. This treatment restored p21(WAF1/Cip1) , induced Beclin-1, and repressed cyclin D1. In addition, sustained suppression of SIRT7 reduced the in vivo tumor growth rate in a mouse xenograft model. To explore mechanisms in SIRT7 regulation, microRNA (miRNA) profiling was carried out. This identified five significantly down-regulated miRNAs in HCC. Bioinformatics analysis of target sites and ectopic expression in HCC cells showed that miR-125a-5p and miR-125b suppressed SIRT7 and cyclin D1 expression and induced p21(WAF1/Cip1) -dependent G1 cell cycle arrest. Furthermore, treatment of HCC cells with 5-aza-2'-deoxycytidine or ectopic expression of wildtype but not mutated p53 restored miR-125a-5p and miR-125b expression and inhibited tumor cell growth, suggesting their regulation by promoter methylation and p53 activity. To show the clinical significance of these findings, mutations in the DNA binding domain of p53 and promoter methylation of miR-125b were investigated. Four out of nine patients with induced SIRT7 carried mutations in the p53 gene and one patient showed hypermethylation of the miR-125b promoter region. CONCLUSION: Our findings suggest the oncogenic potential of SIRT7 in hepatocarcinogenesis. A regulatory loop is proposed whereby SIRT7 inhibits transcriptional activation of p21(WAF1/Cip1) by way of repression of miR-125a-5p and miR-125b. This makes SIRT7 a promising target in cancer therapy. (HEPATOLOGY 2013).

DBC1 does not function as a negative regulator of SIRT1 in liver cancer.

The putative tumor suppressor, DBC1 (deleted in breast cancer-1), was recently found to negatively regulate SIRT1 in vitro and in vivo, but the mechanism whereby DBC1 regulates SIRT1 in liver cancer remains to be elucidated. In this study, it was found that although the expression of DBC1 and SIRT1 was not aberrantly regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, these proteins were highly overexpressed in a subset of HCC tissues compared with surrounding non-cancer tissues. In liver cancer, DBC1 and SIRT1 were found to be positively correlated. Inactivation of DBC1 or SIRT1 reduced SNU-182 (a liver cancer cell line) proliferation as determined by MTT viability assays. Notably, although DBC1 functions as a negative regulator of SIRT1 in A549 lung cancer cells since it suppresses the deacetylase activity of the p53 protein, it did not affect the p53 deacetylase activity of SIRT1 in SNU-182 cells. Taken together, we conclude that DBC1 is associated with SIRT1 in HCC, but that it does not inhibit SIRT1.