Circ_0002669 promotes osteosarcoma tumorigenesis through directly binding to MYCBP and sponging miR-889-3p.

Circular RNAs (circRNAs) are a class of highly multifunctional single-stranded RNAs that play crucial roles in cancer progression, including osteosarcoma (OS). Circ_0002669, generated from the dedicator of cytokinesis (DOCK) gene, was highly expressed in OS tissues, and negatively correlated with OS patient survival. Elevated circ_0002669 promoted OS cell growth and invasion in vivo and in vitro. By biotin pulldown and mass spectroscopy, we found that circ_0002669 directly bound to MYCBP, a positive regulator of c-myc, to prevent MYCBP from ubiquitin-mediated proteasome degradation. In addition, circ_0002669 interacted with miR-889-3p and served as a miRNA sponge to increase the expression of MYCBP, as determined by luciferase assays and RNA immunoprecipitation. Functional rescue experiments indicated MYCBP acted as a key factor for circ_0002669- and miR-889-3p-regulated OS cell proliferation and migration. Increased expression of c-myc-associated genes, such as CCND1, c-Jun and CDK4, were found in circ_0002669- and MYCBP-overexpressing OS cells. Our data thus provide evidence that circ_0002669 promotes OS malignancy by protecting MYCBP from protein ubiquitination and degradation and blocking miR-889-3p-mediated inhibition of MYCBP expression.

A tumor suppressor protein encoded by circKEAP1 inhibits osteosarcoma cell stemness and metastasis by promoting vimentin proteasome degradation and activating anti-tumor immunity.

BACKGROUND: Osteosarcoma (OS) is one of most commonly diagnosed bone cancer. Circular RNAs (circRNAs) are a class of highly stable non-coding RNA, the majority of which have not been characterized functionally. The underlying function and molecular mechanisms of circRNAs in OS have not been fully demonstrated. METHOD: Microarray analysis was performed to identify circRNAs that are differentially-expressed between OS and corresponding normal tissues. The biological function of circKEAP1 was confirmed in vitro and in vivo. Mass spectrometry and western blot assays were used to identify the circKEAP1-encoded protein KEAP1-259aa. The molecular mechanism of circKEAP1 was investigated by RNA sequencing and RNA immunoprecipitation analyses. RESULTS: Here, we identified a tumor suppressor circKEAP1, originating from the back-splicing of exon2 of the KEAP1 gene. Clinically, circKEAP1 is downregulated in OS tumors and associated with better survival in cancer patients. N6-methyladenosine (m6A) at a specific adenosine leads to low expression of circKEAP1. Further analysis revealed that circKEAP1 contained a 777 nt long ORF and encoded a truncated protein KEAP1-259aa that reduces cell proliferation, invasion and tumorsphere formation of OS cells. Mechanistically, KEAP1-259aa bound to vimentin in the cytoplasm to promote vimentin proteasome degradation by interacting with the E3 ligase ARIH1. Moreover, circKEAP1 interacted with RIG-I to activate anti-tumor immunity via the IFN-γ pathway. CONCLUSION: Taken together, our findings characterize a tumor suppressor circKEAP1 as a key tumor suppressor regulating of OS cell stemness, proliferation and migration, providing potential therapeutic targets for treatment of OS.

LncRNA WAC-AS1 promotes osteosarcoma Metastasis and stemness by sponging miR-5047 to upregulate SOX2.

Cancer stemness and osteosarcoma (OS) malignant progression are closely associated. However, the molecular mechanisms underlying this association have not been fully demonstrated. Long noncoding RNAs (lncRNAs) are an intriguing class of widely prevalent endogenous RNAs involved in OS progression, the vast majority of which have not been characterized functionally. Here, we identified tumor promoter lncRNA WAC-AS1 to be highly expressed in OS tumors and associated with worse survival. Further analysis revealed that WAC-AS1 increased tumorsphere formation of OS cells and promoted metastasis, as confirmed by cell proliferation, transwell and wound healing assays. MiR-5047 was identified as a downstream target of WAC-AS1. Subsequently, based on bioinformatics analysis, RIP assay and luciferase reporter assay, SOX2 mRNA was verified as a target of miR-5047. WAC-AS1 enhanced OS cell proliferation and stemness via acting as a ceRNA by binding to miR-5047, thereby increasing SOX2 expression. In addition, SOX2 bound to the promoter region of WAC-AS1 and promoted its transcription, thereby forming a positive feedback loop to regulate OS malignancy. Taken together, our findings show WAC-AS1 is a tumor promoter and a key regulator of OS cell stemness and metastasis via a miR-5047/SOX2 axis.

Methionine can reduce the sublethal risk of Chlorantraniliprole to honeybees (Apis mellifera L.): Based on metabolomics analysis.

Bees, essential for pollination in agriculture and global economic growth. However, the great wax moth (Galleria mellonella, GWM), a Lepidopteran insect, poses a substantial threat to bee colonies, contributing to a global decline in bee populations. Chlorantraniliprole (CH) is one of the primary insecticide used to control GWM due to its efficacy and low toxicity to bees. To improve beekeeping safety and reduce the risk of GWM developing resistance to prolonged use of CH, we investigated the potential of combining methionine (MET) which has been found to have insecticidal activity against certain Lepidoptera pests, with chlorantraniliprole for use in the apiculture industry. This study assessed the combined effects of MET and CH on GWM and honeybees by employing the maximum concentration of MET (1 %, w/w), previously reported as safe for honeybees, and the practical concentration of CH (1 mg/kg) for GWM control. The results revealed limited acute lethal toxicity of MET to GWM and honeybees, whereas the combined chronic exposure of MET and CH (MIX) led to significant synergistic lethal effects on GWM mortality. Nevertheless, the protective effect of MET on honeybees exposed to CH was significant under chronic exposure. Potential mechanisms underlying the synergistic actions of MET and CH may stem from MET-induced protection of the "Cysteine and methionine" and the "Glycine, serine, and threonine" metabolism pathways. Furthermore, immune stress mitigation was also observed in honeybee immune-related gene transcripts treated by the combination of MET and CH under both acute and chronic exposure. The effects of MET on CH activity in GWM and honeybees are likely due to metabolic regulation. This study suggests the potential of developing MET as a promising biopesticide or protective agent in the future.

[Clinical observation of electroacupuncture with different frequencies in treatment of hemiplegic shoulder pain after stroke].

OBJECTIVE: To observe the clinical efficacy on hemiplegic shoulder pain (HSP) after stroke treated with electroacupuncture (EA) under different frequencies. METHODS: A total of 105 patients with HSP after stroke were randomly divided into a manual acupuncture group (35 cases, 2 cases dropped off), an EA continuous wave group (35 cases, 3 cases dropped off) and an EA disperse-dense wave group (35 cases). The conventional rehabilitation therapy was delivered in the three groups. Additionally, acupuncture was applied to Jianyu (LI 15), Jianzhen (SI 9), Jianliao (TE 14) and Jianqian (Extra) etc. on the affected side in the manual acupuncture group. In the EA continuous wave group and the EA disperse-dense wave group, besides the treatment as the manual acupuncture group, the electric stimulation was attached to two pairs of acupoints, i.e. Jianyu (LI 15) and Jianliao (TE 14), and Quchi (LI 11) and Shousanli (LI 10), with 15 Hz continuous wave, and 2 Hz/ 100 Hz disperse-dense wave, respectively. The treatment was given once daily, 5 times a week, for 4 weeks consecutively. The score of visual analogue scale (VAS) before treatment and after 2 and 4 weeks of treatment, as well as the passive range of motion (PROM) of shoulder forward flexion and PROM of shoulder abduction, muscle strength of the upper limb, the score of modified Barthel index (MBI) and the score of Fugl-Meyer assessment (FMA) before and after treatment were observed in each group. RESULTS: Compared with before treatment, VAS scores were reduced after 2 and 4 weeks of treatment in each group (P<0.05); and VAS scores after 4 weeks of treatment were lower than those after 2 weeks of treatment (P<0.05). After 2 and 4 weeks of treatment, VAS score in either the EA continuous wave group or the EA disperse-dense wave group was lower compared with the manual acupuncture group (P<0.05). After 4 weeks of treatment, VAS score in the EA disperse-dense wave was lower than that of the EA continuous wave group (P<0.05). Compared with before treatment, PROM of the shoulder forward flexion and abduction on the affected side after treatment was enlarged (P<0.05), the muscle strength of the upper limb was increased (P<0.05), and the scores of MBI and FMA were increased (P<0.05) in the patients of each group. After treatment, in the EA continuous wave group and the EA disperse-dense wave group, PROM of the shoulder forward flexion on the affected side was higher (P<0.05), the muscle strength of the upper limb was stronger (P<0.05) when compared with the manual acupuncture group; and the scores of MBI and FMA in the EA disperse-dense wave group were higher than those of the manual acupuncture group (P<0.05). CONCLUSION: Electroacupuncture is superior to manual acupuncture in the analgesic effect and comprehensive rehabilitation effect in the patients with HSP after stroke. The therapeutic effect obtained by electroacupuncture with 2 Hz/100 Hz disperse-dense wave is better than that with 15 Hz continuous wave.

A Review on Micro-LED Display Integrating Metasurface Structures.

Micro-LED display technology has been considered a promising candidate for near-eye display applications owing to its superior performance, such as having high brightness, high resolution, and high contrast. However, the realization of polarized and high-efficiency light extraction from Micro-LED arrays is still a significant problem to be addressed. Recently, by exploiting the capability of metasurfaces in wavefront modulation, researchers have achieved many excellent results by integrating metasurface structures with Micro-LEDs, including improving the light extraction efficiency, controlling the emission angle to achieve directional emission, and obtaining polarized Micro-LEDs. In this paper, recent progressions on Micro-LEDs integrated with metasurface structures are reviewed in the above three aspects, and the similar applications of metasurface structures in organic LEDs, quantum dot LEDs, and perovskite LEDs are also summarized.

Research on control strategy of vehicle stability based on dynamic stable region regression analysis.

The intervention time of stability control system is determined by stability judgment, which is the basis of vehicle stability control. According to the different working conditions of the vehicle, we construct the phase plane of the vehicle's sideslip angle and sideslip angular velocity, and establish the sample dataset of the stable region of the different phase planes. To reduce the complexity of phase plane stable region division and avoid large amount of data, we established the support vector regression (SVR) model, and realized the automatic regression of dynamic stable region. The testing of the test set shows that the model established in this paper has strong generalization ability. We designed a direct yaw-moment control (DYC) stability controller based on linear time-varying model predictive control (LTV-MPC). The influence of key factors such as centroid position and road adhesion coefficient on the stable region is analyzed through phase diagram. The effectiveness of the stability judgment and control algorithm is verified by simulation tests.

Research on automatic emergency steering collision avoidance and stability control of intelligent driving vehicle.

In view of the need for emergency steering to avoid collision when the vehicle is in a dangerous scene, and the stability control of the vehicle during collision avoidance. This paper proposes a planning and control framework. A path planner considering the kinematics and dynamics of the vehicle system is used to formulate the safe driving path under emergency conditions. LQR lateral control algorithm is designed to calculate the output steering wheel angle. On this basis, adaptive MPC control algorithm and four-wheel braking force distribution control algorithm are designed to achieve coordinated control of vehicle driving stability and collision avoidance safety. The simulation results show that the proposed algorithm can complete the steering collision avoidance task quickly and stably.

PITX1 suppresses osteosarcoma metastasis through exosomal LINC00662-mediated M2 macrophage polarization.

Paired-like homeodomain transcription factor 1 (PITX1) is frequently downregulated in cancers, including osteosarcoma (OS). However, its role in OS remains unknown. Therefore, we aimed to explore the functions and potential mechanisms of PITX1 in OS malignant progression. Elevated PITX1 suppressed OS cell proliferation and migration, based on transwell, proliferation, and colony formation assays. Pathway enrichment analysis of differentially-expressed genes between PITX1-overexpressing and control OS cells indicated that PITX1 expression was associated with the FAK/Src and PI3k/Akt signaling pathways. Mechanistically, ubiquitination assays and rescue experiments showed that PITX1 interacted with transcription factor STAT3, leading to decreased STAT3 transcriptional activity, which repressed the expression of LINC00662. Specific knockdown of LINC00662 reduced the tumor growth and invasion of OS cells induced by downregulated PITX1. Moreover, exosomal LINC00662, derived from PITX1 knockdown OS cell lines activated M2 macrophages in cell co-culture assays. M2 macrophage secreted several cytokines, among which CCL22 was found to cause OS cell EMT. Collectively, our data indicate that PITX1 suppresses OS cell proliferation and metastasis by downregulating LINC00662. Moreover, LINC00662 can be packaged into OS cell-derived exosomes to mediate M2 macrophage polarization to promote OS metastasis via CCL22.

Distribution and source identification of polychlorinated naphthalenes in bees, bee pollen, and wax from China.

Polychlorinated naphthalenes (PCNs) are highly toxic and persistent organic pollutants that can cause adverse effects in the environment and on human health. PCNs have been detected in remote areas because of their long-range transportation. Bees and bee products are commonly used as biomonitors for various pollutants in the environment. However, information on PCNs in apiaries is scarce. The aim of this study was to evaluate the occurrences of PCNs in bees and bee products from apiaries located in different geographical regions of China, and to identify potential pollution sources and assess exposure risks to humans. Our results showed that the average Σ75PCNs concentrations in bees, pollen, and wax were 74.1, 96.3, and 141 pg/g dry weight, respectively. The homologue and congener profiles of PCNs in bees, pollen, and wax were similar, and di- and tri-chlorinated naphthalenes (>60%) were the predominant homologues. The concentrations and distributions of PCNs in bees, pollen, and wax varied among different geographical regions, but their occurrences were correlated with PCN metallurgical sources in China. The health risks of PCNs in pollen were evaluated, and both carcinogenic and non-carcinogenic risks of PCNs exposure to humans through the diet were low.

Acaricide flumethrin-induced sublethal risks in honeybees are associated with gut symbiotic bacterium Gilliamella apicola through microbe-host metabolic interactions.

Flumethrin is one of the few acaricides that permit the control of Varroa disease or varroosis in bee colonies. However, flumethrin accumulates in hive products. We previously discovered that sublethal doses of flumethrin induce significant physiological stress in honeybees (Apis mellifera L.), however its potential impacts on the honeybee gut microenvironment remains unknown. To fill this gap, honeybees were exposed to a field-relevant concentration of flumethrin (10 µg/L) for 14 d and its potential impacts on gut system were evaluated. The results indicated that flumethrin triggered immune responses in the gut but had limited effects on survival and gut microbial composition. However, survival stress drastically increased in bees exposed to antibiotics, suggesting that the gut microbiota is closely related to flumethrin-induced dysbiosis in the bee gut. Based on a non-targeted metabolomics approach, flumethrin at 10 µg/L considerably altered the composition of intestinal metabolites, and we discovered that this metabolic stress was closely linked with a reduction of gut core bacterial endosymbiont Gilliamella spp. through a combination of microbiological and metabolomics investigations. Finally, an in vitro study showed that while flumethrin does not directly inhibit the growth of Gilliamella apicola isolates, it does have a significant impact on the glycerophospholipid metabolism in bacteria cells, which was also observed in host bees. These findings indicated that even though flumethrin administered at environmental relevant concentrations does not significantly induce death in honeybees, it still alters the metabolism balance between honeybees and the gut symbiotic bacterium, G. apicola. The considerable negative impact of flumethrin on the honeybee gut microenvironment emphasizes the importance of properly monitoring acaricide to avoid potential environmental concerns, and further studies are needed to illustrate the mode of action of bee health-gut microbiota-exogenous pesticides.

Erratum: H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts: Erratum.

[This corrects the article DOI: 10.7150/thno.51245.].

PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p.

BACKGROUND: Emerging evidence has demonstrated that RNA-binding protein dysregulation is involved in esophageal squamous cell carcinoma (ESCC) progression. However, the role of poly (A) binding protein cytoplasmic 1 (PABPC1) in ESCC is unclear. We therefore aimed to explore the functions and potential mechanisms of PABPC1 in ESCC progression. METHODS: PABPC1 expression was characterized using immunohistochemistry and qRT-PCR in ESCC tissues and cell lines. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were used to detect histone acetylation in the promoter region of PABPC1. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of PABPC1 in ESCC angiogenesis and malignant procession. RESULTS: PABPC1 expression was upregulated in ESCC tissues compared with in normal esophageal epithelial tissues. Elevated PABPC1 expression was correlated with tumor cell differentiation and poor prognosis in patients. Sp1 and p300 cooperated to increase the level of H2K37ac in the PABPC1 promoter. Functionally, PABPC1 overexpression enhanced esophageal squamous cell proliferation and invasion by activating the IFN/IFI27 signaling pathway. PABPC1 interacted with eIF4G to increase the stability of IFI27 mRNA by competing with RNA exosomes in ESCC. Furthermore, PABPC1/IFI27 could increase miR-21-5p expression to enable exosomal delivery of miR-21-5p to human umbilical vein endothelial cells to increase angiogenesis via inhibiting CXCL10. CONCLUSION: PABPC1 plays a critical role in ESCC malignant progression by interacting with eIF4G to regulate IFI27 mRNA stability and promote angiogenesis via exosomal miR-21-5p/CXCL10. Taken together, our results suggest that PABPC1 is a promising therapeutic target for ESCC.

The miR-19b-3p-MAP2K3-STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most refractory malignancies worldwide. Mitogen-activated protein kinase 3 (MAP2K3) has a contradictory role in tumor progression, and the function and expression patterns of MAP2K3 in ESCC remain to be determined. We found that MAP2K3 expression to be downregulated in ESCC, and MAP2K3 downregulation correlated with clinically poor survival. MAP2K3 inhibited ESCC cell proliferation and invasion in vitro and in vivo. MAP2K3 suppressed STAT3 expression and activation. Mechanistically, MAPSK3 interacted with MDM2 to promote STAT3 degradation via the ubiquitin-proteasome pathway. Furthermore, exosomal miR-19b-3p derived from the plasma of patients with ESCC could suppress MAP2K3 expression to promote ESCC tumorigenesis. STAT3 was found to bind to the MIR19B promoter and increased the expression of miR-19b-3p in ESCC cells. In summary, our results demonstrated that the miR-19b-3p-MAP2K3-STAT3 feedback loop regulates ESCC tumorigenesis and elucidates the potential of therapeutically targeting this pathway in ESCC.

H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts.

Background: Collagen type VI alpha 1 (COL6A1) has been found to be dysregulated in several human malignancies. However, the role of COL6A1 in osteosarcoma (OS) progression remains largely unclear. Here, we aimed to explore the clinical significance and biological involvement of COL6A1 in the OS cell migration and invasion. Material and Methods: We used immunohistochemistry, qRT-PCR and western blot to detect the expression of COL6A1 in 181 OS patient samples. Chromatin immunoprecipitation (ChIP) and PCR were carried out to verify the regulatory interaction of p300, c-Jun and COL6A1 promoter. The invasion and migration function of COL6A1 in OS was detected in vitro and in vivo. RNA sequence was performed to detect the downstream pathway of COL6A1, and then co-immunoprecipitation (co-IP), ubiquitination assays and rescue experiments were performed to determine the regulatory effect of COL6A1 and signal transducers and activators of transcription (STAT1). Exosomes derived from OS cell lines were assessed for the ability to promote cancer progression by co-cultured assay and exosomes tracing. Results: COL6A1 was commonly upregulated in OS tissues, especially in lung metastasis tissues, which was associated with a poor prognosis. c-Jun bound p300 increased the enrichment of H3K27ac at the promoter region of the COL6A1 gene, which resulted in the upregulation of COL6A1 in OS. Overexpression of COL6A1 promoted OS cell migration and invasion via interacting with SOCS5 to suppress STAT1 expression and activation in an ubiquitination and proteasomal degradation manner. Most interestingly, we found that exosomal COL6A1 derived from OS cells convert normal fibroblasts to cancer-associated fibroblasts (CAFs) by secreting pro-inflammatory cytokines, including IL-6 and IL-8. The activated CAFs could promote OS cell invasion and migration by mediating TGF-ß/COL6A1 signaling pathway. Conclusion: Our data demonstrated that upregulation of COL6A1 activated by H3K27 acetylation promoted the cell migration and invasion by suppressing STAT1 pathway in OS cells. Moreover, COL6A1 can be packaged into OS cell-derived exosomes and activate CAFs to promote OS metastasis.

Multiple Fractures of Cervical Vertebrae Combined with Arcuate Foramen and Vertebral Artery Occlusion: A Case Report and Literature Review.

BACKGROUND: The arcuate foramen is a complete or partial bony bridge over the vertebral artery groove of atlas. The mechanism of the arcuate foramen is not clearly understood. Omission of the arcuate foramen sometimes causes lethal iatrogenic injury during spinal surgery. CASE PRESENTATION: We describe a patient who was diagnosed with multiple fractures of the cervical vertebrae, arcuate foramen, and right vertebral artery occlusion based on clinical and radiological exams. After conservative treatment, he resumed a normal and productive life. CONCLUSIONS: Arcuate foramen is a common variation that causes symptoms such as dizziness, headache, and migraine. If the patient does not develop severe symptoms, conservative treatment can achieve very good results without the necessity to remove the bone bridge. When serious symptoms occur, surgical treatment to resect the bony ridges can relieve the symptoms dramatically.

Room Temperature Versus Warm Irrigation Fluid Used for Patients Undergoing Arthroscopic Shoulder Surgery: A Systematic Review and Meta Analysis.

PURPOSE: The aim of this study was to analyze whether warm irrigation fluid could reduce postoperative adverse effects in patients undergoing arthroscopic shoulder surgery compared with room temperature irrigation fluid. DESIGN: A systematic review and meta-analysis of clinical trials was performed. METHODS: A computerized search of electronic databases was performed. The inclusion criteria were studies comparing the clinical effects of room temperature and warm irrigation fluid on patients undergoing arthroscopic shoulder surgery. FINDINGS: Warm irrigation fluid reduced the degree of core body temperature drop and the incidence of hypothermia. A statistically lower incidence of shivering also occurred in the warm irrigation fluid group. CONCLUSIONS: The use of warm irrigation fluid better maintains core body temperature and reduces incidence of shivering than room temperature irrigation fluid. Therefore, warm irrigation fluid is a better choice for arthroscopic shoulder surgery.

Promoter methylation and clinical significance of GPX3 in esophageal squamous cell carcinoma.

BACKGROUND: Glutathione peroxidase 3 (GPX3) provides critical protection against reactive oxygen species (ROS) in cells. Downregulation of GPX3 may contribute to carcinogenesis of esophageal squamous cell carcinoma (ESCC), but the mechanisms are not clear. MATERIALS AND METHODS: We examined the differences in gene expression between ESCC and normal esophageal epithelial, by using GEO datasets, and collected 136 ESCC tumors and adjacent normal tissues to confirm our findings. GPX3 expression was measured, at the mRNA and protein levels, by qRT-PCR, Western Blot and immunohistochemistry (IHC). RESULTS: GPX3 mRNA and protein levels were 3.3-fold higher in normal epithelium compared with case-matched ESCC tissues. There was no significant correlation between clinical parameters and expression levels of GPX3 in ESCC. Promoter methylation of the GPX3 gene correlated with decreased expression. CONCLUSION: Downregulation of GPX3 might be a key factor in the process of ESCC carcinogenesis.

STAT1 inhibits STAT3 activation in esophageal squamous cell carcinoma.

BACKGROUND: Signal transducer and activator of transcription (STAT) 1 is an important transcription factor and has been reported to be a tumor suppressor in many types of cancer. However, another STAT family member, STAT3, is considered to be an oncogene. The cross-talk between STAT1 and STAT3 in cancer has not been fully demonstrated. MATERIALS AND METHODS: Esophageal squamous cell carcinoma (ESCC) was used as a model to examine STAT1-STAT3 cross-regulation in cancer. We detected STAT1-STAT3 binding by co-immunoprecipitation (co-IP) and measured the transcription activity by using a luciferase reporter gene. DNA binding was detected by a DNA probe. Expression of STAT1 and STAT3 in ESCC was detected by immunohistochemistry. RESULTS: We found that STAT1 attenuated STAT3 activity upon oncostatin M treatment by decreasing STAT3 transcription activity and DNA binding ability of STAT3. Furthermore STAT3 downregulation increased the phosphorylation and transcriptional activation of STAT1. Finally, STAT1 expression and STAT3 expression were negatively correlated in ESCC cases. CONCLUSION: Altogether, this paper demonstrated STAT1 and STAT3 cross-regulation in ESCC and proposed that STAT3 downregulation and/or STAT1 accumulation may be a therapeutic approach to treat ESCC.