Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials.

BACKGROUND: The comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. METHODS: Prospective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. RESULTS: A total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67-0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9-67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64-0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65-0.92, p=0.004) and 0.79 (95 % CI: 0.65-0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. CONCLUSIONS: Our findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.

HOXC10 promotes esophageal squamous cell carcinoma progression by targeting FOXA3 and indicates poor survival outcome.

Background: Esophageal cancer is one of the most unknown and deadliest cancers in the world. Although recent studies have identified some mutations linked to the development of squamous cell carcinoma of the esophagus (ESCC), the specific role of HomeoboxC10 (HOXC10) in the pathogenesis still requires further investigation. Methods: Agilent mRNA single-channel gene expression was employed to identify genome-wide gene signatures in ESCC. These signatures were also verified using qRT-PCR, immunohistochemical staining as well as Western blot. The biological functions of HOXC10 were further investigated through cellular studies conducted on ESCC cells. Survival analysis was conducted utilizing the Kaplan-Meier method. The GEPIA database and the STRING website were utilized to predict the potential targets that bind to HOXC10. Co-immunoprecipitation assays were performed to investigate the binding interaction between HOXC10 and Forkhead Box A3 (FOXA3). Animal models were established to analyze the effects of HOXC10 silencing on tumorigenesis in vivo. Results: The expression levels of HOXC10 mRNA were found to be upregulated in ESCC. Survival analysis revealed a significant association between abnormally elevated levels of HOXC10 mRNA and an unfavorable prognosis in patients with ESCC. In vitro studies revealed that the knockdown of HOXC10 expression resulted in the inhibition of the proliferation, invasion, and migrating ability of ESCC cells through the upregulation of FOXA3. Furthermore, tumor-bearing mouse models studies demonstrated that HOXC10 through knockdown techniques significantly suppressed ESCC tumor growth. HOXC10 was found to enhance the activation of the MAPK signaling pathway by regulating FOXA3 in ESCC cells. Conclusion: These results support a key role for HOXC10 in the tumorigenesis of ESCC by upregulating FOXA3 via the MAPK pathway and highlight its potential as a promising diagnostic and prognostic marker for ESCC.

RGS16 regulates Hippo-YAP activity to promote esophageal cancer cell proliferation and migration.

Esophageal Squamous Cell Carcinoma (ESCC) is a common malignant tumor of digestive tract, accounting for 90% of all pathological types of esophageal cancer. Despite the rapid development of multi-disciplinary treatment such as surgery, chemotherapy, radiotherapy and chemoradiotherapy, the prognosis of patients with ESCC is still poor. Regulators of G-protein signaling (RGSs) are involved in the processes of various cancers. The expression levels of its family member RGS16 are abnormally elevated in a variety of tumors, but its role in ESCC is still unclear. We found that RGS16 expression is aberrantly increased in ESCC tissues and correlated with poor prognosis of ESCC patients from The Cancer Genome Atlas (TCGA) database and our collected ESCC tissues. Moreover, knockdown of RGS16 in two ESCC cells could indeed inhibit their proliferation and migration. We further explored the molecular mechanism of RGS16 in ESCC, and the correlation analysis from TCGA database showed that the mRNA levels of RGS16 was positively correlated with that of CTGF and CYR61, two target genes of Hippo-YAP signaling. Consistently, RGS16- knockdown significantly inhibited the expression of CTGF and CYR61 in ESCC cells. We found that the phosphorylation levels of LATS1 and YAP were significantly increased and YAP translocated into the cytoplasm after depletion of RGS16 in ESCC cells. Also, RGS16-knockdown promoted the interaction between LATS1 and upstream kinase MST1. In addition, reintroduction of a constitutive active YAP5A mutant significantly rescued CTGF expression and cell proliferation in RGS16-knockdown cells. Together, our work revealed that RGS16 promoted YAP activity through disrupting the interaction between LATS1 and MST1, thus promoting the proliferation and migration of ESCC cells.

Competitive adsorption of lead and cadmium onto nanoplastics with different charges: Two-dimensional correlation spectroscopy study.

The competitive adsorption ability and mechanisms of lead (Pb2+) and cadmium (Cd2+) by nanoplastics (NPs) with positive charges (PS-NH2) and negative charges (PS-SO3H) were investigated by using batch adsorption experiments coupled with the two-dimensional correlation spectroscopy (2D-COS) method. The adsorption isotherm results showed that PS-SO3H exhibited a higher adsorption capacity for Pb2+ or Cd2+ compared to PS-NH2. The adsorption affinity of NPs for Pb2+ was higher than that of Cd2+. The competitive adsorption results showed that Pb2+ had a more pronounced negative effect on the adsorption of Cd2+. The adsorption capacities of NPs were affected by the surface charge and solution pH. Electrostatic force was the main factor influencing PS-SO3H to capture Pb2+ and Cd2+, while chelation was the main mechanism between PS-NH2 and metals. The functional groups of NPs played significant roles in the sorption of Pb2+ or Cd2+ according to the FTIR spectra and 2D-COS analysis. This study provided new insights into the impact of NPs on the transport of other pollutants.

Co-Removal Effect and Mechanism of Cr(VI) and Cd(II) by Biochar-Supported Sulfide-Modified Nanoscale Zero-Valent Iron in a Binary System.

This study aimed to explore the co-removal effect and mechanism of Cr(VI) and Cd(II) with an optimized synthetic material. The toxicity and accumulation characteristics of Cr(VI) and Cd(II) encountered in wastewater treatment areas present significant challenges. In this work, a rational assembly of sulfide-modified nanoscale zero-valent iron (SnZVI) was introduced into a biochar (BC), and a Cr(VI)-Cd(II) binary system adsorbent with high efficiency was synthesized. When the preparation temperature of the BC was 600 °C, the molar ratio of S/Fe was 0.3, the mass ratio of BC/SnZVI was 1, and the best adsorption capacities of BC-SnZVI for Cr(VI) and Cd(II) in the binary system were 58.87 mg/g and 32.55 mg/g, respectively. In addition, the adsorption mechanism of BC-SnZVI on the Cr(VI)-Cd(II) binary system was revealed in depth by co-removal experiments, indicating that the coexistence of Cd(II) could promote the removal of Cr(VI) by 9.20%, while the coexistence of Cr(VI) could inhibit the removal of Cd(II) by 43.47%. This work provides a new pathway for the adsorption of Cr(VI) and Cd(II) in binary systems, suggesting that BC-SnZVI shows great potential for the co-removal of Cr(VI) and Cd(II) in wastewater.

Transferrin receptors/magnetic resonance dual-targeted nanoplatform for precise chemo-photodynamic synergistic cancer therapy.

Various drug delivery strategies to improve cancer therapeutic efficacy have been actively investigated. One major challenge is to improve the targeting ability. Here elaborately designed nanocarriers (NCs) named as Tf-5-ALA-PTX-NCs are demonstrated to address this problem. In this nanostructure, paclitaxel (PTX) and 5-aminolevulinic acid (5-ALA) were co-encapsulated within magnetic nanocarriers to achieve synergistic chemotherapy and photodynamic therapy, while transferrin (Tf) was conjugated with modified copolymer Pluronic P123 and embedded in the surface of the nanocarriers, which endows nanocarriers with Tf targeting and magnetic targeting to enhance the anti-tumor outcome. Results demonstrated that Tf-5-ALA-PTX-NCs significantly enhanced the targeting drug delivery to MCF-7 cells and synergistically induced apoptosis and death of MCF-7 cells in vitro and highly efficient tumor ablation in vivo. Intriguingly, Tf-5-ALA-PTX-NCs have a controllable "on/off" switch to enhance the drug release. The dual-targeted nanocarriers would be a promising versatile anti-tumor drug delivery and imaging-guided cancer chemo-photodynamic synchronization therapy strategy.

Distribution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Soils of a Steel Enterprise in East China.

To meet the goal of sustainable development, many large steel enterprises in China have been relocated, leaving serious polycyclic aromatic hydrocarbon (PAH) pollution problems at the abandoned sites. In this study, the spatial distribution and potential health risks of PAHs in soils of a large steel enterprise in East China were studied. The total concentrations of 16 PAHs ranged from 93.96 to2.61E + 05 µg/kg. A total of 54.84% of the samples reached the level of severe pollution, with coking plants and iron works showing much more serious problems than other areas. The contribution levels of PAHs with high molecular weights were high, especially those of 4-ring PAHs. The toxic equivalent concentrations exceeded the values recommended by the Canadian guide. The average carcinogenic risk value of the whole region was greater than 10-6, indicating high carcinogenic risk. The above assessment indicates that the area must be remediated before further development occurs.

Biosorption capacity of Mucor circinelloides bioaugmented with Solanum nigrum L. for the cleanup of lead, cadmium and arsenic.

The biosorption and bioaugmentation performances of Mucor circinelloides were investigated under different contact time, initial metal(loid) concentration and species. The microbe-plant interaction appeared synergistic with enhancing plant growth and alleviating oxidative damages induced by lead, cadmium and arsenic. The bioaugmentation with M. circinelloides led to significant immobilization on lead, cadmium and arsenic as indicated by the decreases of metal(loid) transfer and bioavailability in plant-microbe aqueous system. Lead, cadmium and arsenic were mainly allocated on cell wall and a few parts entered into intercellular system, suggesting cell wall adsorption and intracellular bioaccumulation served as the main mechanisms of M. circinelloides. The adsorption kinetics and isotherms on lead, cadmium and arsenic were fitted well with the pseudo-second-order and Langmuir models, with the maximum adsorption capacities of 500, 15.4 and 29.4 mg·g-1 fungal biomass at pH 6.0 and 25 â„ƒ. The optimum initial concentration and contact time were 300-10-20 mg·L-1 and 2 h. This study provides a basis for M. circinelloides as a promising adsorbent and bioaugmented agent for the cleanup of soil/aqueous environment contaminated with lead, cadmium and arsenic.

Tumor-Secreted Exosomal lncRNA POU3F3 Promotes Cisplatin Resistance in ESCC by Inducing Fibroblast Differentiation into CAFs.

Cancer-associated fibroblasts (CAFs), an activated subpopulation of fibroblasts, occupy a central position in the tumor microenvironment and have been shown to promote chemoresistance in multiple cancer types by secreting inflammatory cytokines. Herein, we report that tumor-secreted exosomal long non-coding RNAs (lncRNAs) can regulate cisplatin resistance in esophageal squamous cell carcinoma (ESCC) through transformation of normal fibroblasts (NFs) to CAFs. Primary CAFs and matched NFs were isolated from tumor tissues and matched normal esophageal epithelial tissues of ESCC patients. Fluorescence microscopy and qRT-PCR were used to investigate the transportation of exosomal lncRNAs from ESCC cells to NFs. To identify the specific lncRNAs involved, 14 ESCC-related lncRNAs were measured in NFs after incubation with exosomes from ESCC cells. We demonstrated that lncRNA POU3F3 can be transferred from ESCC cells to NFs via exosomes and that it mediated fibroblast activation. Activated fibroblasts further promoted proliferation and cisplatin resistance of ESCC cells through secreting interleukin 6 (IL-6). Moreover, our clinical data showed that high levels of plasma exosomal lncRNA POU3F3 correlated significantly with lack of complete response and poor survival in ESCC patients. Therefore, these data demonstrate that lncRNA POU3F3 is involved in cisplatin resistance in ESCC and that this effect is mediated through exosomal lncRNA POU3F3-induced transformation of NFs to CAFs.

Depletion of LAMP3 enhances PKA-mediated VASP phosphorylation to suppress invasion and metastasis in esophageal squamous cell carcinoma.

Metastasis is still a major cause of cancer-related mortality. Lysosome-associated membrane protein 3 (LAMP3) has been implicated in the invasiveness and metastasis of multiple cancer types; however, the underlying mechanisms are unclear. In this study, we found that LAMP3 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and that this increased expression positively correlated with lymph node metastasis. Depletion of LAMP3 dramatically suppressed the motility of ESCC cells in vitro and experimental pulmonary and lymph node metastasis in vivo. Importantly, knockdown of LAMP3 increased the level of phosphorylated VASP(Ser239), which attenuated the invasive and metastatic capability of ESCC cells. We identified that cAMP-dependent protein kinase A (PKA) was responsible for the phosphorylation of VASP at Ser239. Consistently, silencing of PKA regulatory subunits diminished Ser239 phosphorylation on VASP and restored the motility capacity of LAMP3-depleted ESCC cells. In conclusion, we uncovered a previously unknown role of LAMP3 in promoting cellular motility and metastasis in ESCC.

Circ-SLC7A5, a potential prognostic circulating biomarker for detection of ESCC.

Circular RNAs (circRNAs), resulting from the non-canonical splicing of linear pre-mRNAs, have permanently altered our perspectives toward cancer recently, especially in carcinogenesis and cancer progression. However, the roles of circRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In the current study, circRNAs expression profiles are screened in ESCC, using plasma samples from 10 ESCC patients, including different TNM stages and 5 normal controls. Characteristics of circRNAs including length, types, and the possibility of binding to proteins are analyzed. Candidate tumor-related circRNAs are then quantitated in ESCC tissues, plasmas and cell lines. ESCC tissues can secret circRNAs into plasma and patients with high plasma circ-SLC7A5 are associated with high TNM stage, tending to have shorter overall survival than those with high levels. In addition, the biological characteristics of circ-SLC7A5 including location, miRNAs binding, m6A modification were analyzed. Our study reveals a novel prognosis biomarker of circ-SLC7A5, providing a preliminary landscape of circRNA expression for detection of ESCC.

Circ-ZDHHC5 Accelerates Esophageal Squamous Cell Carcinoma Progression in vitro via miR-217/ZEB1 Axis.

Circular RNA (circRNA) exhibits a covalently closed circular conformation and is structurally stable. Nevertheless, the precise effects exerted by circRNA in esophageal squamous cell carcinoma (ESCC) remains uncertain. circRNA was ascertained by a human circRNA array study and was confirmed by the quantification of reverse transcriptase polymerase reactions. A luciferase reporter, fluorescence in situ hybridization experiment was exploited to explore the interaction between circ-ZDHHC5 and miR-217. The function of circ-ZDHHC5 was determined by siRNA-mediated knockout of circ-ZDHHC5 in in vitro proliferation, migration, and invasion. circ-ZDHHC5, rather than linear ZDHHC5 mRNA, rose in the tissues of patients with ESCC, plasma, and ESCC cell lines in comparison with normal controls. Knockdown of circ-ZDHHC5 inhibited tumorigenesis in ESCC cells, and the co-transfection of si-circ-ZDHHC5 and miR-217 mimics further enhanced the above effect. Noticeably, the present study showed that circ-ZDHHC5 was an miR-217 sponge that modulated the expression of zinc finger E-box binding homeobox 1 (ZEB1), further facilitating ESCC tumorigenesis. As revealed by this study, circ-ZDHHC5 can act as a new potential circular biomarker for detecting ESCC. It provides a novel perceptivity for the treatment of ESCC suggesting that circ-ZDHHC5 could impact on ESCC progression by sponging miR-217 with ZEB1.

Long noncoding RNA PANDA promotes esophageal squamous carcinoma cell progress by dissociating from NF-YA but interact with SAFA.

Esophageal squamous cell carcinoma (ESCC) is one of the major global health problems, especially in Asia. Long non-coding RNAs (lncRNAs) have been increasingly identified and characterized in almost every aspect of biology, especially in cancer biology. This research desires to explore the regulatory mechanism of lncRNA PANDA (PANDA) on ESCC process. Quantitative real-time PCR (qRT-PCR) was carried out to detect the PANDA expression, which was up-regulated in matched cancerous tissues and adjacent noncancerous tissues from 134 patients and 9 ESCC cell lines. Higher expression of PANDA in ESCC tissues was associated with TNM stage, advanced clinical stage, and shorter overall survival of ESCC patients by MTT, EDU, colony formation assay and flow cytometry in KYSE180 and KYSE450 cells. Exogenous down-regulation of PANDA expression significantly suppressed ESCC cells proliferation and colony formation by arresting G1-S checkpoint transition in vitro, and retarded the development of tumors in vivo. Meanwhile, qRT-PCR and western blot assays showed that depletion of PANDA reduced E2F1, cyclinD1, cyclinD2, cyclinE1 and Bcl-2 expression. RIP showed the interaction between PANDA and NF-YA or SAFA. Our findings suggested that, PANDA drifted away from NF-YA to promote the expression of NF-YA-E2F1 co-regulated proliferation-promoting genes, and to limit the cell apoptosis. In addition, PANDA binds SAFA to switch on the tumor proliferation program through CyclinD1/2-Cyclin E1 and Bcl-2 pathways. PANDA could serve as a potential prognostic biomarker and therapeutic target for ESCC.

Up-regulation of SPC25 promotes breast cancer.

In this study, expression of the SPC25 gene was characterized in breast cancer (BC), and its effects on BC development and progression, functions in BC cells, and potential underlying mechanisms were examined. Data from TCGAportal and FIREBROWSE indicated that SPC25 was upregulated in BC tissues compared to normal tissues, and CANCERTOOL indicated that higher SPC25 mRNA levels were associated with increased probability of recurrence and poorer survival in BC patients. BC patients with higher SPC25 expression displayed shorter distant metastasis-free survival, relapse-free survival, and overall survival. Colony formation and CCK-8 experiments confirmed that SPC25 promoted proliferation of BC cells. Single-cell analysis indicated that SPC25 is associated with cell cycle regulation, DNA damage and repair, and BC cell proliferation. SPC25 knockdown suppressed proliferation of BC cells. MiRNAs, circRNAs, RNA-binding proteins, transcription factors, and immune factors that might interact with SPC25 mRNA to promote BC were also identified. These findings suggest that SPC25 levels are higher in more malignant BC subtypes and are associated with poor prognosis in BC patients. In addition, DNA methyltransferase inhibitor and transcription factors inhibitor treatments targeting SPC25 might improve survival in BC patients.

Cyclin A1 is associated with poor prognosis in oesophageal squamous cell carcinoma.

Dysregulation of cyclin A1 (CCNA1) is implicated in the carcinogenesis, progression and metastasis of many types of solid tumours. In the present study, an mRNA single-channel expression profile chip experiment revealed that the CCNA1 mRNA levels in oesophageal squamous cell carcinoma (ESCC) were increased >10-fold compared with those in the adjacent non-cancer tissues. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry analyses were performed to additionally investigate the role of CCNA1 in the development and progression of ESCC in patients treated by radical resection of the oesophagus. The association between CCNA1 mRNA expression and the clinicopathological parameters of patients with ESCC was statistically analysed. The results indicated that upregulation of CCNA1 occurred in ~70% of patients with ESCC, and increased CCNA1 mRNA expression was significantly associated with advanced clinical stage, lymph node metastasis, invasiveness and poor clinical outcome, including disease-free survival and overall survival rates. Taken together, the data suggested that CCNA1 had an important function in ESCC development and progression, and may serve as a prognostic biomarker and therapeutic target in ESCC.

Correction: HOTAIR regulates HK2 expression by binding endogenous miR-125 and miR-143 in oesophageal squamous cell carcinoma progression.

[This corrects the article DOI: 10.18632/oncotarget.21195.].

Transferrin-functionalised microemulsion co-delivery of ß-elemene and celastrol for enhanced anti-lung cancer treatment and reduced systemic toxicity.

In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries ß-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that ß-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of ß-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with ß-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.

Mass spectrometry analysis reveals aberrant N-glycans in colorectal cancer tissues.

Aberrant glycosylation is strongly correlated with the development of various cancers. Tumor-associated carbohydrate antigens, including N-glycans, are predominantly expressed on the tumor cell surface. Because the incidence of colorectal cancer is high in China, we investigated aberrant N-glycans from colorectal cancer tissues (CRC) in Chinese patients. By Linear ion trap quadrupole-electrospray ionization mass spectrometry, we performed glycomic assays on N-glycans obtained from solid CRC tissues and paired peritumoral tissues. In total, aberrant N-glycans were expressed in the colorectal tumor tissues. Specifically, seven bisecting structures (M/Z 9732+, 10602+, 10752+, 11622+, 11772+, 12642+, 13522+) decreased, M/Z 10552+ (two-antennae complex N-glycan) and M/Z 12792+ (three-antennae complex N-glycan) decreased, M/Z 10132+ and M/Z 11162+ (high-mannose N-glycan) increased, and M/Z 12282+ (bifucosylated N-glycan) increased. To evaluate the MS profile data, several statistical tools were applied, including student's t test, orthogonal partial least squares discriminant analysis and receiver operating characteristic curve. The measurement of the degree of bisecting N-glycans had an area under the curve value of 0.823. Interestingly, we observed that the bisecting N-glycans decreased with the tumor stages. This phenomenon was not found in esophageal squamous cell carcinoma, in which the bisecting N-glycans had no change. Thus, the expression of bisecting N-glycans may be an interesting point in the study of colorectal cancer.

Up-regulation of circ-SMAD7 inhibits tumor proliferation and migration in esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidences demonstrate that circular RNAs (circRNAs) play an important role in the development and progression of human cancers. Nevertheless, the functions and molecular mechanism of circRNAs in esophageal squamous cell carcinoma (ESCC) tumorigenesis are largely unknown. The purpose of this research is to investigate the expression and potential role of a new circular RNA named circ-SMAD7 on ESCC carcinogenesis. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure circ-SMAD7 expression amount in both ESCC plasmas and tissues. Then the correlation between the expression of circ-SMAD7 and clinicopathological features was analyzed. Furthermore, by loss-of-function and gain-of-function experiments in ESCC cells, a functional analysis of circ-SMAD7 on ESCC cell proliferation and migration was performed. RESULTS: The expression of circ-SMAD7 was validated to be significantly down-regulated in ESCC plasmas in comparison with normal controls, showing a high negative correlation with TNM stage (P = 0.000) and lymphatic metastasis (P = 0.000). Moreover, circ-SMAD7 was significantly down-regulated in ESCC tissues compared to adjacent normal tissues. Furthermore, Loss-of-function and gain-of-function experiments revealed that the expression level of circ-SMAD7 affected the proliferation and migration of ESCC cell lines. CONCLUSION: Our study firstly exposed that over-expressioncirc-SMAD7, an influential regulator in cancer progression, can inhibit tumor proliferation and migration in ESCC and have the potential of becoming a biomarker for the diagnosis and therapy of ESCC.

Circ-TTC17 Promotes Proliferation and Migration of Esophageal Squamous Cell Carcinoma.

BACKGROUND: Circular RNAs (circRNAs), a special class of noncoding RNAs with the characteristic of covalent closed-loop structure, have been widely found in various organisms. Growing evidence has shown that circRNAs play a crucial role in regulating biological functions of cancers. However, the specific role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains largely unknown. AIM: The present study aims to investigate the effects of circ-TTC17 in ESCC clinical samples as well as cells. METHODS: Sanger sequencing and agarose gel electrophoresis were used to verify the specificity of circ-TTC17. Expression levels of circ-TTC17 in ESCC cells, plasma, and tissues were measured by quantitative real-time polymerase chain reaction. A colony formation experiment, CCK-8 assay, and wound-healing assay were applied to detect the functions of circ-TTC17 in KYSE30 and KYSE450 cells. A nucleus-cytoplasm fractionation experiment was used to probe the location of circ-TTC17 in ESCC cells. Finally, a network of circ-TTC17 with its targeted miRNAs interactions and corresponding mRNAs was analyzed and framed by bioinformatics. RESULTS: The expression level of circ-TTC17 was found to be significantly higher in ESCC cells, plasma, and tissues compared with normal cases. In vitro experiments indicated that circ-TTC17 promoted proliferation and migration of ESCC cells. Bioinformatics predictions showed that circ-TTC17 might regulate progress of ESCC by acting as a sponge for microRNAs (miRNAs). CONCLUSIONS: The results of this study demonstrate that upregulated circ-TTC17 plays a key role in promoting proliferation and migration of ESCC cells and has potential to become a novel biomarker for diagnosis, treatment, and prognosis of ESCC in the future.