NDRG2 acts as a negative regulator of the progression of small-cell lung cancer through the modulation of the PTEN-AKT-mTOR signalling cascade.

N-myc downstream-regulated gene 2 (NDRG2) has been recognised as a negative regulator of the progression of numerous tumours, yet its specific role in small-cell lung carcinoma (SCLC) is not fully understood. The purpose of the current study was to investigate the biological role and mechanism of NDRG2 in SCLC. Initial investigation using the Gene Expression Omnibus (GEO) dataset revealed marked downregulation of NDRG2 transcripts in SCLC. The decreased abundance of NDRG2 in SCLC was verified by examining clinical specimens. Increasing NDRG2 expression in SCLC cell lines caused significant changes in cell proliferation, cell cycle progression, colony formation, and chemosensitivity. NDRG2 overexpression decreased the levels of phosphorylated PTEN, AKT and mTOR. In PTEN-depleted SCLC cells, the upregulation of NDRG2 did not result in any noticeable impact on AKT or mTOR activation. Additionally, the reactivation of AKT reversed the antitumour effects of NDRG2 in SCLC cells. Notably, increasing NDRG2 expression retarded the growth of SCLC cell-derived xenografts in vivo. In conclusion, NDRG2 serves as an inhibitor of SCLC, and its cancer-inhibiting effects are achieved through the suppression of AKT/mTOR via the activation of PTEN. This work suggests that NDRG2 is a potential druggable target for SCLC treatment.

Zinc finger protein 367 exerts a cancer-promoting role in small cell lung cancer by influencing the CIT/LATS2/YAP signaling cascade.

A remarkable cancer-related role of zinc finger protein 367 (ZNF367) has been demonstrated in multiple malignancies. However, whether ZNF367 has a role in small-cell lung cancer (SCLC) remains unexplored. The purpose of this work was to explore the potential role and mechanism of ZNF367 in SCLC. In silico analysis using the Gene Expression Omnibus (GEO) dataset revealed high levels of the ZNF367 transcript in SCLC. Examination of clinical tissues confirmed the significant abundance of ZNF367 in SCLC tissues compared with adjacent non-malignant tissues. The genetic depletion of ZNF367 in SCLC cells led to remarkable alterations in cell proliferation, the cell cycle, colony formation and chemosensitivity. Mechanistically, ZNF367 was shown to regulate the activation of yes-associated protein (YAP) associated with the up-regulation of phosphorylated large tumour suppressor kinase 2 (LATS2). Further investigation revealed that ZNF367 affected the LATS2-YAP cascade by regulating the expression of citron kinase (CIT). Re-expression of constitutively active YAP diminished the tumour-inhibiting function of ZNF367 depletion. Xenograft experiments confirmed the tumour-inhibiting effect of ZNF367 depletion in vivo. In summary, our results demonstrate that the inhibition of ZNF367 displays anticancer effects in SCLC by inhibiting YAP activation, suggesting it as a potential druggable oncogenic target.

Surgical Treatment for Isolated Closed Multi-metatarsal Fractures: At Least 2-Year Outcomes in 79 Feet.

Multimetatarsal fractures are a particular type possibly associated with worse functional outcomes. Existing studies are scarce, fragmented, and lack control for confounders. This study aimed to explore the functional prognosis of isolated closed extra-articular multimetatarsal fractures and the different outcomes between the plate-screw and K-wire fixation. This retrospective study included 79 patients who underwent surgery for isolated closed extra-articular multimetatarsal fractures from May 2017 to December 2020. We recorded baseline characteristics. The primary outcome measure was Visual Analogue Scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) score, and Foot and Ankle Outcome Score (FAOS). Exploratory correlation analysis of the variables with VAS, AOFAS score, and FAOS was performed. The differences between the plate-screw group (n = 58) and K-wire group (n = 21) were compared. Seventy-nine patients (79 feet) were included with a follow-up of (47.3 ± 12.7) months (range, 26-70). Full weight bearing time was (11.7±5.3) weeks. VAS was (1.4±1.8) points, AOFAS score was (86.4±13.3) points, and FAOS was (79.0±11.1) points. Complications were observed in 17 cases (21.5%). According to exploratory correlation analysis, VAS was weakly associated with fixation method and gender, AOFAS was weakly associated with fixation method, FAOS was weakly associated with trauma mechanism. When the plate-screw group (n = 58) was compared with the K-wire group (n = 21), we found the former was superior to the latter in terms of full weight bearing time, VAS, AOFAS score, and malunion rate (all p < .05). FAOS was nonsignificant (p = .056). Operative treatment of isolated closed extra-articular multimetatarsal fractures showed good mid-term results. Plate-screw fixation was associated with faster rehabilitation as well as a lower malunion rate. The mid-term follow-up results showed patients with plate-screw fixation had better VAS and AOFAS scores.

Transcriptional Circuitry of NKX2-1 and SOX1 Defines an Unrecognized Lineage Subtype of Small-Cell Lung Cancer.

Rationale: The current molecular classification of small-cell lung cancer (SCLC) on the basis of the expression of four lineage transcription factors still leaves its major subtype SCLC-A as a heterogeneous group, necessitating more precise characterization of lineage subclasses. Objectives: To refine the current SCLC classification with epigenomic profiles and to identify features of the redefined SCLC subtypes. Methods: We performed unsupervised clustering of epigenomic profiles on 25 SCLC cell lines. Functional significance of NKX2-1 (NK2 homeobox 1) was evaluated by cell growth, apoptosis, and xenograft using clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9)-mediated deletion. NKX2-1-specific cistromic profiles were determined using chromatin immunoprecipitation followed by sequencing, and its functional transcriptional partners were determined using coimmunoprecipitation followed by mass spectrometry. Rb1flox/flox; Trp53flox/flox and Rb1flox/flox; Trp53flox/flox; Nkx2-1flox/flox mouse models were engineered to explore the function of Nkx2-1 in SCLC tumorigenesis. Epigenomic landscapes of six human SCLC specimens and 20 tumors from two mouse models were characterized. Measurements and Main Results: We identified two epigenomic subclusters of the major SCLC-A subtype: SCLC-Aα and SCLC-Aσ. SCLC-Aα was characterized by the presence of a super-enhancer at the NKX2-1 locus, which was observed in human SCLC specimens and a murine SCLC model. We found that NKX2-1, a dual lung and neural lineage factor, is uniquely relevant in SCLC-Aα. In addition, we found that maintenance of this neural identity in SCLC-Aα is mediated by collaborative transcriptional activity with another neuronal transcriptional factor, SOX1 (SRY-box transcription factor 1). Conclusions: We comprehensively describe additional epigenomic heterogeneity of the major SCLC-A subtype and define the SCLC-Aα subtype by the core regulatory circuitry of NKX2-1 and SOX1 super-enhancers and their functional collaborations to maintain neuronal linage state.

The high-risk features and effect of postoperative radiotherapy on survival for patients with surgically treated stage IIIA-N2 non-small cell lung cancer.

OBJECTIVES: Although postoperative radiotherapy (PORT) could reduce the incidence of local recurrence in patients with IIIA-N2 non-small cell lung cancer (NSCLC), the role of PORT on survival in patients with surgically treated stage IIIA-N2 NSCLC remains controversial. Therefore, this study was designed to evaluate the effect of PORT on survival for patients with surgically treated stage IIIA-N2 NSCLC. MATERIALS AND METHODS: This study population was chosen from the Surveillance, Epidemiology, and End Results database. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) and cancer special survival (CSS) outcomes. To balance baseline characteristics between the non-PORT group and PORT group, propensity score matching (PSM) with 1:1 propensity nearest-neighbor match by 0.001 matching tolerance was conducted by R software. Furthermore, a Kaplan-Meier curve was used to visualize the OS and CSS between the PORT group and non-PORT group survival probability. RESULTS: Of all evaluated cases, 4511 with IIIA-N2 NSCLC were eligible for inclusion, of which 1920 were enrolled into the PORT group. On univariate analysis and multivariate analysis, sex, age, year of diagnosis, race, histologic type, T stage, PORT, use of chemotherapy, and positive regional nodes were significantly associated with OS and CSS in IIIA-N2 NSCLC (P < 0.05). However, PORT was not significantly associated with OS (univariate HR = 0.92, 95%CI 0.85-0.99, P = 0.02; multivariate HR = 1.01, 95%CI 0.93-1.08, P = 0.91) and CSS (univariate HR = 0.92, 95%CI 0.85-1.01, P = 0.06; multivariate HR = 1.103 95%CI 0.94-1.12, P = 0.56) in IIIA-N2 NSCLC. Meanwhile, after PSM, neither OS nor CSS did differ significantly between the non-PORT group and PORT group (OS HR = 1.08, 95%CI 0.98-1.19, P = 0.12; CSS HR = 1.10, 95%CI 0.99-1.23, P = 0.07). CONCLUSION: PORT did not contribute to a survival benefit in patients with surgically treated stage IIIA-N2 NSCLC.

Circular RNA SMARCA5 suppressed non-small cell lung cancer progression by regulating miR-670-5p/RBM24 axis.

Circular RNAs (circRNAs) have good stability and long half-life in blood and other body fluid, and possess regulatory effects on various biological processes as miRNA/RNA-binding protein sponges, or by competing endogenous RNA, indicating their great potential as biomarkers or targets of cancer therapy. In this study, we mainly explored the role and mechanism of circular RNA SMARCA5 (circsSMARCA5) in non-small cell lung cancer (NSCLC). Quantitative RT-PCR was applied to measure the expression levels of genes, and then, the relationships among circsSMARCA5, microRNA-670-5p (miR-670-5p), and RBM24 were further analyzed. Animal and cell experiments were performed to explore the functions of circsSMARCA5 in NSCLC cells. The results showed that circsSMARCA5 was expressed at low level in NSCLC tissues and cells, while miR-670-5p had high level in NSCLC tissues. Dual luciferase reporter assay verified that miR-670-5p was the target of circsSMARCA5, and RBM24 has the binding site of miR-670-5p. Further analysis showed that circsSMARCA5 could negatively regulate miR-670-5p and had positive relationship with RBM24. Moreover, circsSMARCA5 obviously inhibited tumor growth in vivo, reduced cell proliferation and increased cell apoptosis in vitro, while miR-670-5p mimic or RBM24 knockdown could reverse these effects. Thus, circsSMARCA5 may serve as an NSCLC suppressor by regulating the miR-670-5p/RBM24 axis, and it may have the potential to be a biomarker or therapeutic target for NSCLC.

Endoscopic ultrasonography for preoperative staging of esophageal carcinoma.

OBJECTIVE: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) in preoperative staging of esophageal carcinoma (EC). MATERIAL AND METHODS: A total of 86 surgical patients with EC who were confirmed by endoscopy and biopsy underwent preoperative TN staging with EUS examination. The EUS findings were compared with surgical pathologic results. RESULTS: The accuracy of EUS in T and N staging of EC was 82.6% and 84.9%, respectively. While determining whether EC invades the muscularis propria or outer membrane, EUS had the favorable sensitivity, specificity, positive predictive value and negative predictive value. The short-axis diameter of lymph nodes of 5mm had high sensitivity and negative predictive value to determine malignance with low specificity and positive predictive value. The short-axis diameter of 10mm presented the satisfactory sensitivity, specificity, positive predictive value and negative predictive value. CONCLUSION: EUS can accurately determine the TN staging of EC and provide a reliable basis for the treatment of EC.

The crucial role of miR-126 on suppressing progression of esophageal cancer by targeting VEGF-A.

BACKGROUND: miR-126 is a key regulator of oncogenic processes. It is functionally linked to cellular proliferation, survival and migration. Vascular endothelial growth factor A (VEGF-A), which is regarded as a tumorgenesis activator, could directly target miR-126 in several tumors. However, the mechanism in esophageal cancer remains unclear. METHODS AND RESULTS: In this study, the expression of miR-126 and VEGF-A were assessed in esophageal cancer tissues and esophageal cancer cell lines. We found that miR-126 has significantly lower expression in esophageal cancer tissues and esophageal cancer cell lines than in healthy tissues, while the expression of VEGF-A is high. Luciferase reporter assays were performed to investigate the relationship between VEGF-A and miR-126. We confirmed that VEGF-A is a target for miR-126. Furthermore, the proliferation of esophageal cancer cells with miR-126 overexpression and miR-126 knockdown was monitored using the MTT assay. The results showed that miR-126 could inhibit esophageal cancer cell proliferation in vitro. The effect of miR-126 was also detected in BALB/c nude mice with transplanted esophageal cancer cells. In vivo study showed that tumor growth was significantly suppressed by miR-126 overexpression. CONCLUSIONS: We believe that restoring miR-126 levels may be a promising therapeutic approach in cases of esophageal cancer.

Exploring temporal trends and burden of traumatic shoulder dislocation: a global perspective.

Objective: To explore the geographical and temporal trends of traumatic shoulder dislocation, describe the association between the social and demographic factors and the health burden due to traumatic shoulder dislocation, and further investigate its causes. Methods: Data on traumatic shoulder dislocation was collected from the Global Burden of Disease 2019, spanning the years 1990 to 2019. The epidemiology and disease burden were examined at global, regional, and national levels. Additionally, the age and gender patterns were analyzed, followed by an investigation into the primary causes. Lastly, the study studied the correlation between age-standardized rates and the socio-demographic index (SDI). Results: Over a span of 30 years, both the crude and age-standardized rates of incidence and years lived with disability (YLDs) rates for all genders displayed a slight fluctuating downward trend. The incidence and YLDs rates in males were consistently higher than those in females. The study analyzed both incidence and YLDs rates of the global, regional, and national of traumatic shoulder dislocations from 1990 to 2019, as well as the temporal trends. Among males, the highest incidence rate was observed in young adulthood, while females exhibited the highest incidence rate in old age. This pattern was mirrored in the YLDs rate. Falls were identified as the main cause contributing to the disease burden related to traumatic shoulder dislocations. Moreover, a positive correlation was found between the age-standardized rates and SDI. Conclusion: The disease burden of traumatic shoulder dislocation has not significantly decreased from 1990 to 2019. The incidence and YLD rates are associated with age, gender, and SDI. A thorough examination of the disease burden contributes to the efficient allocation and utilization of resources, as well as the development of targeted and effective intervention strategies.

Is the diagnostic validity of conventional radiography for Lisfranc injury acceptable?

BACKGROUND: Lisfranc injuries mainly involve the tarsometatarsal joint complex and are commonly misdiagnosed or missed in clinical settings. Most medical institutions prefer to use conventional radiography. However, existing studies on conventional radiographs in Lisfranc injury lack a large population-based sample, influencing the validity of the results. We aimed to determine the diagnostic validity and reliability of conventional radiography for Lisfranc injury and whether computed tomography can alter clinical decision-making. METHODS: This retrospective study included 307 patients with, and 100 patients without, Lisfranc injury from January 2017 to December 2019. Diagnosis was confirmed using computed tomography. A senior and junior surgeon independently completed two assessments of the same set of anonymised conventional radiographs at least 3 months apart. The surgeons were then asked to suggest one of two treatment options (surgery or conservative treatment) for each case based on the radiographs and subsequently on the CT images. RESULTS: All inter- and intra-observer reliabilities were moderate to very good (all κ coefficients > 0.4). The mean (range) true positive rate was 81.8% (73.9%-87.0%), true negative rate was 90.0% (85.0%-94.0%), false positive rate was 10.0% (6.0%-15.0%), false negative rate was 18.2% (13.0%-26.1%), positive predictive value was 96.1% (93.8%-97.8%), negative predictive value was 62.4% (51.5%-69.7%), classification accuracy was 83.8% (76.7%-88.2%), and balanced error rate was 14.1% (10.2%-20.5%). Three-column injuries were most likely to be recognized (mean rate, 92.1%), followed by intermediate-lateral-column injuries (mean rate, 81.5%). Medial-column injuries were relatively difficult to identify (mean rate, 60.7%). The diagnostic rate for non-displaced injuries (mean rate, 76.7%) was lower than that for displaced injuries (mean rate, 95.5%). The typical examples are given. A significant difference between the two surgeons was found in the recognition rate of non-displaced injuries (p = 0.005). The mean alteration rate was 21.9%; the senior surgeon tended to a lower rate (15.6%) than the junior one (28.3%) (p < 0.001). CONCLUSIONS: The sensitivity, specificity, and classification accuracy of conventional radiographs for Lisfranc injury were 81.8%, 90.0%, and 83.8%, respectively. Three-column or displaced injuries were most likely to be recognized. The possibility of changing the initial treatment decision after subsequently evaluating computed tomography images was 21.9%. The diagnostic and clinical decision-making of surgeons with different experience levels demonstrated some degree of variability. Protected weight-bearing and a further CT scan should be considered if a Lisfranc injury is suspected and conventional radiography is negative.

Nebulized inhalation of LPAE-HDAC10 inhibits acetylation-mediated ROS/NF-κB pathway for silicosis treatment.

Silicosis is a serious silica-induced respiratory disease for which there is currently no effective treatment. Irreversible pulmonary fibrosis caused by persistent inflammation is the main feature of silicosis. As an underlying mechanism, acetylation regulated by histone deacetylases (HDACs) are believed to be closely associated with persistent inflammation and pulmonary fibrosis. However, details of the mechanisms associated with the regulation of acetylated modification in silicosis have yet to be sufficiently established. Furthermore, studies on the efficient delivery of DNA to lung tissues by nebulized inhalation for the treatment of silicosis are limited. In this study, we established a mouse model of silicosis successfully. Differentially expressed genes (DEGs) between the lung tissues of silicosis and control mice were identified based on transcriptomic analysis, and HDAC10 was the only DEG among the HDACs. Acetylomic and combined acetylomic/proteomic analysis were performed and found that the differentially expressed acetylated proteins have diverse biological functions, among which 12 proteins were identified as the main targets of HDAC10. Subsequently, HDAC10 expression levels were confirmed to increase following nebulized inhalation of linear poly(ß-amino ester) (LPAE)-HDAC10 nanocomplexes. The levels of oxidative stress, the phosphorylation of IKKß, IκBα and p65, as well as inflammation were inhibited by HDAC10. Pulmonary fibrosis, and lung function in silicosis showed significant improvements in response to the upregulation of HDAC10. Similar results were obtained for the silica-treated macrophages in vitro. In conclusion, HDAC10 was identified as the main mediator of acetylation in silicosis. Nebulized inhalation of LPAE-HDAC10 nanocomplexes was confirmed to be a promising treatment option for silicosis. The ROS/NF-κB pathway was identified as an essential signaling pathway through which HDAC10 attenuates oxidative stress, inflammation, and pulmonary fibrosis in silicosis. This study provides a new theoretical basis for the treatment of silicosis.

Endothelial glycocalyx in hepatopulmonary syndrome: An indispensable player mediating vascular changes.

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features-intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.

HyProCure for Pediatric Flexible Flatfoot: What Affects the Outcome.

Background: The high success rate, minimal invasion, and safety of subtalar arthroereisis (SA) have made it a primary mode of surgical management for pediatric flexible flatfoot. The HyProCure procedure is a new surgery for SA, However, very few available studies reported the therapeutic effects of the HyProCure procedure, especially in pediatric flexible flatfoot. The main aim of the present study was to investigate the clinical and radiological outcomes of the HyProCure procedure for pediatric flexible flatfoot and analyze the risk factors for therapeutic outcomes and sinus tarsi pain. Methods: In this retrospective cohort study, 69 pediatric flexible flatfoot patients (107 feet) who underwent the HyProCure procedure were included between July 2015 and September 2020. All patients underwent the HyProCure procedure with or without gastrocnemius recession. The Maryland foot score (MFS), visual analog scale (VAS), radiographic data, and complications were assessed at a minimum 1-year follow-up and statistically analyzed. Results: The mean follow-up was 35.9 months (range, 13-73 months). At the last follow-up, VAS (0.64 ± 1.16) was significantly lower than the preoperative VAS (4.06 ± 1.43) (p < 0.001); MFS (90.39 ± 12.10) was significantly higher than the preoperative MFS (71.36 ± 10.25) (p < 0.001). The AP talar-second metatarsal angle (T2MT angle) significantly decreased from 17.0 ± 5.4° preoperatively to 11.4 ± 5.2° at the last follow-up (p < 0.001). The lateral talar-first metatarsal angle (Meary's angle) significantly decreased from 13.8 ± 6.4° preoperatively to 6.3 ± 5.0° at the last follow-up (p < 0.001). The calcaneal declination angle (Pitch angle) significantly increased from 13.5 ± 4.9° preoperatively to 14.8 ± 4.4° at the last follow-up (p < 0.001). Logistic regression analysis indicated that patients with a longer distance from the tail end of the implant exceeding the longitudinal talar bisection line had 275.8% greater odds of MFS < 90. Yet, no risk factors were found in connection with sinus tarsi pain. Conclusions: The HyProCure procedure for pediatric flexible flatfoot achieved satisfactory curative effects with a low complication rate; implant depth was associated with unsatisfactory postoperative outcome.

Lateral approach for insertional Achilles tendinitis with Haglund deformity.

Objective: The study aims to investigate the functional outcome of the lateral approach for insertional Achilles tendinitis (IAT) with Haglund deformity. Methods: From January 2016 to September 2019, 14 cases of IAT with Haglund deformity that resisted conservative treatment received surgery in our department. A lateral approach was used to debride the bony and soft tissue and reattach the insertion of the Achilles tendon. The Visual Analog Scale (VAS), American Orthopedic Foot and Ankle Score (AOFAS), and Victorian Institute of Sport Tendon Study Group-Achilles Tendinopathy score (VISA-A) were used to evaluate clinical outcomes. Result: The mean patient age was 39.57 years at the time of surgery. The mean follow-up was 14.74 months. The mean VAS score significantly decreased from 4.86 ± 0.86 preoperatively to 1.21 ± 1.58 postoperatively (P < 0.001). The mean AOFAS score significantly improved from 66.64 ± 6.23 preoperatively to 90.21 ± 11.50 postoperatively (P < 0.001). The mean preoperative and the last follow-up VISA-A were 66 (range 56.75-69.25) and 86 (range 75.75-97.00) points, respectively (P < 0.05). Conclusion: The lateral approach was effective and safe for IAT with Haglund deformity. Moreover, the mid-term functional outcome was promising. Level of Clinical Evidence: IV.

Effects of Dentin Ablation by a Q-Switching Er:YSGG Laser with a High Pulse Repetition Rate.

Objective: The aim of the study was to evaluate the characteristics of dentin ablation with a high pulse repetition rate Q-switching 2.79 µm laser. Materials and methods: Dentin was ablated using a homemade Q-switching Er:YSGG laser with a high pulse repetition rate. Er:YSGG radiation was applied with a pulse energy of 1 or 10 mJ for 100 or 3 Hz pulse repetition rate, respectively. A scanning electron microscope (SEM) was used to observe the microstructures of dentin samples after ablation. Teeth were irradiated in vitro with a 100 Hz pulse repetition rate under two different modes: free running and Q-switching. A thermocouple was applied to measure the temperature in the pulp cavity during ablation. Results: A 100 or 3 Hz Q-switching laser was used to irradiate dentin for 30 and 100 sec, respectively. There was no significant difference in ablation mass loss between the two conditions. The SEM photographs showed more dentinal tubules and no damage in the ablation area when using the 100 Hz Q-switching laser. The temperature of the pulp cavity was maintained below 41°C when using a Q-switching laser. Conclusions: The Q-switching Er:YSGG laser with a high pulse repetition rate exhibited greater ablation efficiency and better morphology than the low pulse repetition rate Q-switching laser. The experimental results also demonstrate the significant advantage of the Q-switching laser over free-running lasers for protecting dental pulp tissue. The Q-switching Er:YSGG laser with a high pulse repetition rate is expected to become an efficient new dental tool.

TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-ß-catenin signaling.

The Wnt/ß-catenin pathway plays vital roles in diverse biological processes, including cell differentiation, proliferation, migration, and insulin sensitivity. A recent study reported that the DNA-binding transcriptional factor SIX3 is essential during embryonic development in vertebrates and capable of downregulating target genes of the Wnt/ß-catenin pathway in lung cancer, indicating negative regulation of Wnt/ß-catenin activation. However, regulation of the SIX3-Wnt/ß-catenin pathway axis remains unknown. We measured the expression of TRIM27 and SIX3 as well as investigated whether there was a correlation between them in lung cancer tissue samples. Herein, we found that the E3 ubiquitin ligase, TRIM27, ubiquitinates, and degrades SIX3. TRIM27 induces non-small cell lung cancer (NSCLC) cell proliferation and metastasis, and the expression of ß-catenin, S100P, TGFB3, and MMP-9 were significantly inhibited by SIX3. Furthermore, XAV939 is a selective ß-catenin-mediated transcription inhibitor that inhibited TRIM27- and SIX3-mediated NSCLC cell proliferation, migration, and invasion. Clinically, lung tissue samples of cancer patients showed increased TRIM27 expression and decreased SIX3 expression. Taken together, these data demonstrate that TRIM27 acts as an oncogene regulating cell proliferation and metastasis in NSCLC through SIX3-ß-catenin signaling.