An archaeal transcription factor EnfR with a novel 'eighth note' fold controls hydrogen production of a hyperthermophilic archaeon Thermococcus onnurineus NA1.

Thermococcus onnurineus NA1, a hyperthermophilic carboxydotrophic archaeon, produces H2 through CO oxidation catalyzed by proteins encoded in a carbon monoxide dehydrogenase (CODH) gene cluster. TON_1525 with a DNA-binding helix-turn-helix (HTH) motif is a putative repressor regulating the transcriptional expression of the codh gene cluster. The T55I mutation in TON_1525 led to enhanced H2 production accompanied by the increased expression of genes in the codh cluster. Here, TON_1525 was demonstrated to be a dimer. Monomeric TON_1525 adopts a novel 'eighth note' symbol-like fold (referred to as 'eighth note' fold regulator, EnfR), and the dimerization mode of EnfR is unique in that it has no resemblance to structures in the Protein Data Bank. According to footprinting and gel shift assays, dimeric EnfR binds to a 36-bp pseudo-palindromic inverted repeat in the promoter region of the codh gene cluster, which is supported by an in silico EnfR/DNA complex model and mutational studies revealing the implication of N-terminal loops as well as HTH motifs in DNA recognition. The DNA-binding affinity of the T55I mutant was lowered by ∼15-fold, for which the conformational change of N-terminal loops is responsible. In addition, transcriptome analysis suggested that EnfR could regulate diverse metabolic processes besides H2 production.

Pleomorphic dermal sarcoma presenting in a child with Li-Fraumeni syndrome: A case report and review of the literature.

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature.

Can We Forgo Sentinel Lymph Node Biopsy in Women Aged ≥ 50 Years with Early-Stage Hormone-Receptor-Positive HER2-Negative Special Histologic Subtype Breast Cancer?

BACKGROUND: Breast cancer has significant biologic heterogeneity, which influences treatment decisions. We hypothesized that in postmenopausal women (≥ 50 years) with clinical T1-2, N0, hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer of special histology (mucinous, tubular, cribriform, papillary), information from sentinel lymph node biopsy (SLNB) may not change adjuvant therapy recommendations. PATIENTS AND METHODS: We constructed a cohort from the National Cancer Database of women aged ≥ 18 years with cT1-2 N0 HR+ HER2- invasive breast cancer. We calculated the frequency of nodal positivity by histology. We measured the frequency of N2/N3 disease, the distribution of Oncotype DX 21-gene assay recurrence score (ODX RS) across special histology by nodal status, and frequency of chemotherapy use by ODX RS and pathologic N stage. RESULTS: In women with cN0 HR+/HER2- special histologic subtype breast cancer, the likelihood of pathologic nodal positivity is less than 5%, and 99.7% of patients had N0 or N1 disease. Among women aged ≥ 50 years with HR+/HER2- special histologic subtype breast cancer, there was low prevalence of high ODX RS > 25 in both N0 and N1 patients (7% overall). Receipt of chemotherapy correlated with Oncotype DX scores as anticipated, with the lowest use in women with a low/intermediate RS (from 2 to 6% for N0 and 6-24% for N1) and the highest use in women with high risk Oncotype scores (from 74 to 92%). CONCLUSIONS: Our study suggests that SLNB could potentially be omitted in select postmenopausal women with cT1-2 N0 HR+/HER2- special histologic subtype breast cancer when ODX RS is available.

Distribution of cellular remnants of melanocytes in the nail plate: Clue to the diagnosis of subungual melanoma.

BACKGROUND: Previous studies reported that cellular remnants in the nail plate could be a diagnostic clue for subungual melanoma (SUM). We sought to characterize the histopathologic features of cellular remnants in the nail plates of SUM patients. METHODS: A retrospective case-control study was conducted in a single tertiary center from 2012 to 2019. Twenty-three patients with pathologically diagnosed SUM and eight nail matrix nevi (NMN) patients were recruited. The analysis of the nail plate specimens focused on large cellular remnants of melanocytes (LCRMs). Longitudinal linear density and vertical distribution pattern of the LCRMs were scrutinized for possible features distinguishing SUM from NMN. RESULTS: The median linear density of the LCRMs was significantly higher in the SUM samples than in the NMN samples. LCRMs in the SUM samples were more dorsally distributed than those in the NMN samples. In invasive SUM, LCRMs were more likely to be found in the dorsal part of the nail plate compared to SUM in situ. CONCLUSION: Nail plate specimens should not be overlooked in the histopathological examination of melanonychia. High-density LCRMs with more dispersion to the dorsal side might be suggestive of SUM.

Magnesium microneedle patches for under-eye wrinkles.

Microneedling is a common cosmetic procedure for improvement of wrinkles, acne, scars, and other conditions. Various microneedle (MN) patches have been developed as home care therapy for wrinkles and skin texture. Most of them are made of soluble and absorbable needles. To evaluate the efficacy and safety of non-absorbable magnesium (Mg) MN patches on under-eye wrinkles. A total of 20 subjects aged 27-58 years was enrolled in the study. The subjects applied Mg MN patches on the under-eye wrinkle area for 1-2 h every other night for 12 weeks. The evaluation comprised grading by clinicians, measuring the wrinkle index with a facial analyzer, and measuring the dermal thickness of the under-eye area with ultrasonography. Any adverse events and discomfort were addressed during the study. The application of Mg MN patches on under-eye areas showed improvements in under-eye grading scale, wrinkle index, and dermal thickness after 12 weeks. The mean grading scale significantly improved after 8 weeks of application (p < 0.01). The wrinkle index showed significant improvement after 12 weeks on the right under-eye area (p < 0.05). The dermal thickness of the under-eye area tended to increase, but no statistically significant changes were observed. Non-absorbable Mg MN patches can be used for under-eye wrinkles with minimal discomfort.

Hutchinson Sign: Biopsy May Assist in Diagnosis of Subungual Melanoma in Situ.

BACKGROUND: Early and accurate diagnosis of subungual melanoma (SUM) through histopathologic examination is critical, but lack of clinical suspicion leads to delays in diagnosis. Hutchinson sign (HS) can be one of the important clinical indicators for diagnosing SUM. OBJECTIVE: To evaluate the diagnostic value of small biopsies of HS for detecting SUM in situ. METHODS: We retrospectively evaluated 12 patients who were diagnosed as SUM in situ and underwent punch biopsy at HS areas. Clinical features, dermoscopic findings, and histopathologic findings in HS regions were analyzed. RESULTS: In most cases, HS was seen in hyponychium (11/12, 91.7%) with 1 case found in proximal nail fold, and 1 case in both the hyponychium and proximal nail fold. Dermoscopic features of HS showed irregular diffuse pigmentation (12/12, 100%) and parallel ridge pattern (7/12, 58.3%). Histopathologically, all cases showed irregularly scattered atypical melanocytes with hyperchromatic nuclei. Two cases showed subtle changes in melanocytes with little nuclear atypia, but additional section specimen showed more definitive findings of SUM in situ. CONCLUSION: We present a supplementary biopsy technique for diagnosing SUM. Biopsy of HS may help in the diagnosis of SUM.

Dual Clarithromycin and Metronidazole Resistance Is the Main Cause of Failure in Ultimate Helicobacter pylori Eradication.

BACKGROUND/AIM: Antimicrobial resistance significantly affects the cure rate of Helicobacter pylori (H. pylori) eradication. We evaluated the risk factor of failure in ultimate H. pylori eradication and assessed the efficacy of current regimens to overcome antibiotic resistance. METHODS: Patients with H. pylori infection were prospectively enrolled in a single center. They were classified into 3 groups according to the previous history of H. pylori eradication, and antibiotic susceptibility was evaluated by culture and minimum inhibitory concentrations (MICs). RESULTS: Ninety-seven patients were successfully cultured for H. pylori and 81 (83.5%), 7 (7.2%), and 9 (9.3%) were classified into primary resistance, 1st eradication failure, and 2nd or more eradication failure groups; the resistance to clarithromycin (CLA), metronidazole (MET), and levofloxacin increased in the 1st eradication failure (85.7, 57.1, and 42.9%) and 2nd or more eradication failure (88.9, 88.9, and 55.6%) groups. The prevalence of MDR was 21.0% (17/81), 57.1% (4/7), and 88.9% (8/9) in the primary, 1st eradication failure, and 2nd or more eradication failure groups, respectively. In multivariate analysis, dual CLA/MET resistance (CLA/MET-R) (OR = 31.432, 95% CI: 3.094-319.266, p = 0.004) was an independent risk factor for ultimate H. pylori eradication failure. In patients with dual CLA/MET-R, the eradication ratio of concomitant therapy was 57.1% (4/7), whereas that of bismuth-containing quadruple therapy was 27.3% (3/11) (p = 0.350). CONCLUSIONS: Dual CLA/MET-R was the main cause of failure in ultimate H. pylori eradication, and 7-day bismuth quadruple or concomitant regimen would not be suitable for H. pylori eradication in the dual CLA/MET-R group.

Construction of a non-contact community treatment centre for asymptomatic and mildly symptomatic COVID-19 patients during the COVID-19 pandemic.

The explosive outbreak of COVID-19 led to a shortage of medical resources, including isolation rooms in hospitals, healthcare workers (HCWs) and personal protective equipment. Here, we constructed a new model, non-contact community treatment centres to monitor and quarantine asymptomatic and mildly symptomatic COVID-19 patients who recorded their own vital signs using a smartphone application. This new model in Korea is useful to overcome shortages of medical resources and to minimise the risk of infection transmission to HCWs.

Anti-pollution skincare: Research on effective ways to protect skin from particulate matter.

While there is increasing interest in anti-pollution care to particulate matter (PM), there has been no research evaluating the efficacy of skin care products in a real-world setting. Our objective was to find effective ways to protect skin from PM. In total, 64 volunteers whose skin was classified as reactive to PM concentration in the previous study were enrolled. Through split-face study, different combinations of skin care products (barrier cream, barrier cream/micellar water, antioxidant, and antioxidant/micellar water) were applied for 4 weeks during the high-PM period. The biophysical properties were measured, and a facial analysis system was used to evaluate skin condition at days 0, 14, and 28. The concentrations of PM and daily events that may affect skin conditions were also recorded. The mean concentration levels of PM10 and PM2.5 from days 0 to 14 were higher in the barrier cream group than in the antioxidant group. For each group, aside from skin tone in the antioxidant/micellar water group, there were no statistically significant differences in skin measurements before and after the application, which reflects no aggravation in skin condition during high-PM periods. Intergroup analysis showed no differences in skin measurements among the four groups from day 0 to day 14, from day 14 to day 28, and from day 0 to 28. For anti-pollution care, maintaining skin barrier function using barrier cream seems to be sufficient in individuals sensitive to PM.

Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption.

BACKGROUND: Acneiform eruption is the most common cutaneous adverse event associated with cetuximab. As it can affect quality of life and adversely affect chemotherapy schedule, additional medical care is required. OBJECTIVES: To investigate the adherence to and the duration of antibiotic administration to treat cetuximab-induced acneiform eruption. METHODS: Medical data of patients who were referred to the Department of Dermatology were reviewed from January 2013 to June 2018. Dermatologists assessed the severity of acneiform eruption and prescribed tetracycline-class antibiotics according to the severity every 2 or 4 weeks. We investigated the duration and amount of oral antibiotic administration and analyzed the factors that may affect the control of acneiform eruption statistically. RESULTS: A total of 207 of 267 patients referred to the Department of Dermatology showed acneiform eruption; 124 patients were treated with minocycline, 34 patients with doxycycline, 27 patients with both, and 22 patients with topical agents. The mean duration of oral antibiotic medication was 82.7 days. A statistical analysis of the factors that prolonged the use of antibiotics for more than 90 days showed that male and younger age were risk factors. Shorter time interval from starting cetuximab to starting antibiotics was associated with longer duration of antibiotic use, statistically. CONCLUSIONS: Cetuximab-induced acneiform eruption can be well controlled with tetracycline-class antibiotics in about 3 months. It can last longer in male and younger patients. The sooner and the more severe it appears, the longer it can last.

Association between the change of total cholesterol during adolescence and depressive symptoms in early adulthood.

Increasing evidence suggests that serum lipids are associated with depressive symptoms. However, previous studies have mostly employed a cross-sectional design and assessed middle-aged or older adult populations, making it difficult to discern the impact of lipid changes early in life on the development of depression. Accordingly, we sought to investigate changes in blood cholesterol levels during adolescence and the development of depressive symptoms in early adulthood. This prospective cohort study included participants aged 15-16 years from the JS High School Study (JSHS), with an average follow-up of 6 years. Participants had no diagnosed depression at baseline. Multivariable linear regression models were used to estimate associations between changes in total cholesterol during adolescence and depressive symptoms in adulthood. Changes in total cholesterol during adolescence were classified as "consistently low," "decreased," "moderate," "increased," or "consistently high". In men, depressive symptoms were higher in the consistently low (ß = 3.20, p = 0.036) and increased total cholesterol groups (ß = 3.48, p = 0.017), compared with the moderate group. In the consistently high group, although a positive linear association was observed, it lacked statistical significance (ß = 2.71, p = 0.067). While similar tendencies were noted in women, the associations were not statistically significant. Consistently low or increased total cholesterol levels during adolescence may pose an increased risk of depressive symptoms in early adulthood. These findings suggest that different strategies should be adopted to manage the lipid risk factors with consideration of age and sex.

Effect of photobiomodulation therapy on radiodermatitis in a mouse model: an experimental animal study.

This study aimed to evaluate the effect of photobiomodulation (PBM) for prevention of radiodermatitis in an irradiated mouse model and compare the efficacy of PBM using 633- or 830-nm wavelengths. Irradiated mice were randomly distributed into three groups: A (633 nm), B (830 nm), and C (without PBM). On post-irradiation days 7 and 21, we compared acute damage and recovery in treated skin samples to non-irradiated skin using H&E, Masson's trichrome, anti-CD45 and PCNA immunohistochemistry, and a TUNEL assay. Grade 3 radiodermatitis was evident only in group C. Compared with that in group C, the skin in groups A and B had significantly less epidermal hyperplasia, inflammatory cell infiltration, and thinner dermis on day 7 and less inflammatory cell infiltration, fewer apoptotic cells, and thinner dermis on day 21. However, there was no significant difference between groups A and B. This study indicates PBM could prevent severe radiodermatitis by reducing epidermal and dermal damage, inflammation, and apoptosis. There was no difference in PBM efficacy between the 633- and 830-nm wavelengths.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

Moderate to vigorous physical activity participation associated with better quality of life among breast and colorectal cancer survivors in Korea.

BACKGROUND: To investigate the association between physical activity (PA) and quality of life (QoL) among breast and colorectal cancer survivors in Korea. METHODS: A total of 224 cancer survivors (151 breast and 73 colorectal cancers) who completed treatments were recruited. We measured PA level with Godin Leisure-Time Exercise Questionnaire and QoL with European Organization for Research and Treatment of Cancer (EORTC) QLQ C-30. RESULTS: Moderate to vigorous PA was significantly correlated with global QoL (r = .311, p < 0.01), physical functioning (r = .231, p < 0.01), fatigue (r = -.176, p < 0.05), pain (r = -.154, p < 0.05), and dyspnea (r = -.221, p < 0.01) while no correlation was found between light PA and QoL after controlling for potential confounders. When we further divided our participants into four groups by total PA level, we found a strong linear dose-response relationship between higher total PA and better QoL outcomes (p < .001). Compared with participants in the lowest quartile, those in the highest quartile had significantly better score in global QoL (65.8 ± 2.7 vs. 77.6 ± 2.8, p = 0.003), physical functioning (67.2 ± 2.3 vs. 85.3 ± 2.4, p = 0.007), fatigue (35.9 ± 3.2 vs. 23.6 ± 3.2, p = 0.008), pain (22.7 ± 3.3 vs. 13.0 ± 3.4, p = 0.046), and dyspnea (13.7 ± 2.5 vs. 5.9 ± 2.6, p = 0.034). CONCLUSIONS: Higher PA level was associated with better QoL among breast and colorectal cancer survivors in Korea. Increasing PA levels should be included as one of important strategies to improve QoL in cancer survivors.

Characteristics of diffuse retinal nerve fiber layer defects in red-free photographs as observed in optical coherence tomography en face images.

BACKGROUD: To determine whether diffuse retinal nerve fiber layer (RNFL) defects, identified on red-free fundus photographs, could be identified on optical coherence tomography (OCT) en face structural images and to evaluate which factors are related to the different recognition patterns on en face images. METHODS: This retrospective, cross-sectional study included open-angle glaucoma eyes with diffuse RNFL defects in the inferior hemifield, identified in red-free photographs. The corresponding OCT en face structural images were divided into 3 groups: (1) no defect, (2) localized defect, and (3) diffuse defect. We compared the demographic and clinical ocular characteristics among the groups. RESULTS: A total of 209 eyes from 157 patients were included. The distribution of OCT en face images was: no defect, 25 eyes (11.96%); localized defect, 106 eyes (50.72%); diffuse defect, 78 eyes (37.32%). Logistic regression analysis revealed that eyes with greater mean deviation (P = 0.004) and thicker inferior RNFL (P = 0.008) would be included in the no defect and localized defect groups based on OCT en face images, rather than in the diffuse defect group. CONCLUSION: Around half of diffuse RNFL defects identified in the red-free photographs appeared as localized defects in OCT en face images. Mild glaucomatous damage was related to no defect and localized defect groups, classified based on the OCT en face images, in eyes with diffuse photographic RNFL defects. OCT en face images may be helpful in further assessing diffuse RNFL defects seen in red-free photographs in eyes with open-angle glaucoma.

Topical Application of Phlorotannins from Brown Seaweed Mitigates Radiation Dermatitis in a Mouse Model.

Radiation dermatitis (RD) is one of the most common side effects of radiotherapy; its symptoms progress from erythema to dry and moist desquamation, leading to the deterioration of the patients' quality of life. Active metabolites in brown seaweed, including phlorotannins (PTNs), show anti-inflammatory activities; however, their medical use is limited. Here, we investigated the effects of PTNs in a mouse model of RD in vivo. X-rays (36 Gy) were delivered in three fractions to the hind legs of BALB/c mice. Macroscopic RD scoring revealed that PTNs significantly mitigated RD compared with the vehicle control. Histopathological analyses of skin tissues revealed that PTNs decreased epidermal and dermal thickness compared with the vehicle control. Western blotting indicated that PTNs augmented nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathway activation but attenuated radiation-induced NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and inflammasome activation, suggesting the mitigation of acute inflammation in irradiated mouse skin. PTNs also facilitated fast recovery, as indicated by increased aquaporin 3 expression and decreased γH2AX (histone family member X) expression. Our results indicate that topical PTN application may alleviate RD symptoms by suppressing oxidative stress and inflammatory signaling and by promoting the healing process. Therefore, PTNs may show great potential as cosmeceuticals for patients with cancer suffering from radiation-induced inflammatory side effects such as RD.

The First Case of 2019 Novel Coronavirus Pneumonia Imported into Korea from Wuhan, China: Implication for Infection Prevention and Control Measures.

In December 2019, a viral pneumonia outbreak caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV), began in Wuhan, China. We report the epidemiological and clinical features of the first patient with 2019-nCoV pneumonia imported into Korea from Wuhan. This report suggests that in the early phase of 2019-nCoV pneumonia, chest radiography would miss patients with pneumonia and highlights taking travel history is of paramount importance for early detection and isolation of 2019-nCoV cases.

Feasibility of photobiomodulation therapy for the prevention of radiodermatitis: a single-institution pilot study.

Acute radiodermatitis is one of the major complications when radiation therapy (RT) is delivered to the head and neck region in cases of head and neck cancers or lung cancers with supraclavicular lymph node metastasis. In these cases, high dose of RT is generally used so that acute radiodermatitis is observed in more than 90% of patients, and it negatively affects patients' quality of life. In this pilot study, we evaluated the clinical feasibility of photobiomodulation (PBM) therapy before conducting a randomized trial based on the hypothesis that PBM therapy may reduce the severity of radiodermatitis in participants receiving 60 Gy or higher dose. Patients who were to receive 60 Gy or higher dose in the neck were included in the study. Thirty-three patients received PBM therapy three times a week during RT. The severity of radiodermatitis was evaluated by two dermatologists and a radiation oncologist using the modified Common Terminology Criteria for Adverse Events (CTCAE). Patients were followed up until a week after RT. In all patients, 90.6% of planned PBM schedule was completed. There was no significant side effect of PBM therapy. Thirteen (39%) patients showed wet desquamation (CTCAE grade 2b or higher). Only three (9%) of them showed grade 3 toxicity, which is a favorable result compared with previous studies. This pilot study showed that PBM therapy is safe and feasible in the clinic, and it might reduce the severity of radiodermatitis. A randomized trial should be warranted to prove the efficacy of PBM therapy.

Aqueous solubility of beryllium(II) at physiological pH: effects of buffer composition and counterions.

Beryllium ion elicits p53-mediated cell cycle arrest in some types of human cancer cells, and it is a potent inhibitor of GSK3 kinase activity. Paradoxically, Be2+ is regarded to have almost negligible aqueous solubility at physiological pH, due to precipitation as Be(OH)2. This study demonstrates that the interaction of Be2+ with serum proteins greatly increases its effective solubility. In typical serum-supplemented mammalian cell culture medium, Be2+ was soluble up to about 0.5 mM, which greatly exceeds the concentration needed for biological activity. Some biochemical studies require protein-free Be2+ solutions. In such cases, the inclusion of a specific inorganic counterion, sulfate, increased solubility considerably. The role of sulfate as a solubility-enhancing factor became evident during preparation of buffered solutions, as the apparent solubility of Be2+ depended on whether H2SO4 or a different strong acid was used for pH adjustment. The binding behavior of Be2+ observed via isothermal titration calorimetry was affected by the inclusion of sodium sulfate. The data reflect a "Diverse Ion Effect" consistent with ion pair formation between solvated Be2+ and sulfate. These insights into the solubility behavior of Be2+ at physiological and near-physiological pH will provide guidance to assist sample preparation for biochemical studies.

Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling.

Hyaluronic acid synthase 2 (HAS2) is suggested to play a critical role in malignancy and is abnormally expressed in many carcinomas. However, its role in colorectal cancer (CRC) malignancy and specific signaling mechanisms remain obscure. Here, we report that HAS2 was markedly increased in both CRC tissue and malignant CRC cell lines. Depletion of HAS2 in HCT116 and DLD1 cells, which express high levels of HAS2, critically increased sensitivity of radiation/oxaliplatin-mediated apoptotic cell death. Moreover, downregulation of HAS2 suppressed migration, invasion and metastasis in nude mice. Conversely, ectopic overexpression of HAS2 in SW480 cells, which express low levels of HAS2, showed the opposite effect. Notably, HAS2 loss- and gain-of-function experiments revealed that it regulates CRC malignancy through TGF-ß expression and SMAD2/Snail downstream components. Collectively, our findings suggest that HAS2 contributes to malignant phenotypes of CRC, at least partly, through activation of the TGF-ß signaling pathway, and shed light on the novel mechanisms behind the constitutive activation of HAS2 signaling in CRC, thereby highlighting its potential as a therapeutic target.