Radiation-induced inflammatory responses are known to contribute to lung injury, but how these responses occur under ultra-high dose rate FLASH irradiation (FLASH) remains poorly characterized. The present study aimed to compare inflammation-mediated cancer progression in FLASH versus conventional (CONV) irradiation-induced lung injury in mice. Using a modified Varian 23CX clinical accelerator to deliver electron beam FLASH, we performed whole thoracic irradiation in healthy C57BL/6J mice with both FLASH and CONV modalities. While both triggered similar acute inflammatory responses, FLASH resulted in significantly less pulmonary fibrosis at 12 weeks post-irradiation. Acute radiation-induced lung inflammation promoted cancer progression in both groups, with neutrophil recruitment contributing to tumor cell metastasis. During chronic inflammation, however, FLASH led to fewer metastatic colonies than CONV. Further analysis revealed that FLASH accelerated macrophage polarization toward the M2 phenotype during chronic inflammation, whereas CONV promoted M1 polarization. Importantly, FLASH maintained tumor control comparable to CONV while markedly reducing normal tissue toxicity. These results demonstrate that radiation-induced inflammation facilitates cancer progression and suggest that differential macrophage polarization may help explain the distinct lung responses to CONV versus FLASH irradiation. Further studies are needed to elucidate the tissue changes that occur prior to tumor cell seeding in irradiated lungs.

Ultra-high dose rate FLASH Radiotherapy (FLASH-RT) has attracted wide attention because the well-known FLASH effect and the extremely short irradiation time. During FLASH-RT, high radiation doses and dose rate (usually thousands of times compared with conventional radiotherapy (CONV-RT)) are delivered to the tumor area. This novel irradiation technique shows a reduction of normal tissue injury (20-40%) in comparison to CONV-RT. Meanwhile, FLASH-RT maintaining comparable tumor killing effect as CONV-RT. With the progress of basic research on FLASH-RT in reducing radiation-induced injury to normal tissues, clinical trials of FLASH-RT have been carried out across the world. To date, there is no consensus in China focused on the exploration of clinical transformation and application of electron FLASH-RT. Therefore, the China Anti-Cancer Association Radiation Oncology Committee and the Chinese Medical Doctor Association Radiation Oncology Physician Committee gathered a group of experts together to develop this consensus statement. The authors discuss their current views on electron FLASH-RT, demonstrate the unresolved questions, provide insights for the further application of this technology in clinical practice.

BACKGROUND:FLASH irradiation, a technique that delivers prescribed dose at ultra-high dose rate, has been described to alleviate normal tissue injury in multiple animal models. However, the underlying mechanism was not fully understood. PURPOSE:We aimed to investigate whether FLASH irradiation-induced acute lung injury could reduce metastatic colonization compared with conventional (CONV) irradiation. METHODS:Healthy lungs of C57BL/6J male mice were irradiated with either FLASH or CONV, SV2 lung adenocarcinoma cells were intravenously injected and healthy lung volume was monitored using micro-computed tomography (micro-CT). The irradiated tissues (tumor + normal parenchyma) were analyzed by proteomic to identify key regulators of cancer progression. Key proteins were preliminarily validated using real-time quantitative PCR and western blot. Further validation was carried out by inhibiting or promoting neutrophil extracellular traps (NETs) formation within in vivo models. RESULTS:In radiation-induced acute lung injury models, both CONV and FLASH involved in equivalent and enhanced metastatic colonization. Follow-up molecular analysis using proteomic profiling revealed NETs formation involved in cancer progression. Both radiation modalities triggered acute lung injury and inflammatory response with a similar pattern. Inhibiting NETs formation significantly delay tumor metastasis in either FLASH or CONV, whereas stimulating NETs formation markedly accelerate cancer progression. CONCLUSION:These experiments suggest that healthy lung spare does not recapitulate at acute time point after exposure to FLASH. Proteomic analyses suggest a possible role for NETs formation within the tumor microenvironment in deriving cancer cell seeding. NETs formation could be served as a prognostic factor in thoracic cancer.

Objective:Ultra-high dose rate FLASH radiotherapy (FLASH-RT) is emerging as a novel technique to improve the normal tissue tolerance by delivering ultra-high dose rate radiation several orders of magnitude higher than convention radiotherapy. It has been shown in preclinical studies to cause less injury to surrounding normal tissues during radiation treatment, while still maintaining local tumor control. The purpose of this protocol is to evaluate the safety of fractionated FLASH-RT in skin cancer. Method:Patients with superficial skin tumors will be enrolled. The eligible patients will undergo electron FLASH-RT (24-40 Gy/3-5 fractions) to the tumor volume. The primary outcome is to evaluate the safety of FLASH-RT by collecting the acute (< 90 days) skin toxicity adverse events of radiation according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary objectives include late (> 90 days) skin toxicity after FLASH-RT according to CTCAE version 5.0 and treatment response. Discussion:If the results show that delivering FLASH-RT is safe and feasible for skin tumors, further investigation will be conduct to evaluate efficacy of FLASH-RT in a phase II trial. Trial Registration number:ChiCTR2400080935. https://www.chictr.org.cn/showproj.html?proj=220336.

Objective:Ultrahigh-dose-rate radiotherapy (FLASH-RT) has been shown to reduce radiation-induced normal tissue injury in preclinical studies. Here, we describe the first patient worldwide to receive fractionated FLASH-RT. Methods:An elderly male patient was diagnosed with extramammary Paget disease of the scrotum along with multiple lymph node and bone metastases. After 6 cycles of chemotherapy, the disease progressed in the scrotum. The scrotal lesions were evaluated for FLASH-RT. 9 MeV electron FLASH-RT was performed at a dose rate of 120 Gy/s. The field size was 5 cm × 5 cm, and the prescribed dose was 40 Gy in five fractions. Dosimetric verification was performed daily. Treatment response was evaluated at 3-month post FLASH-RT, and normal tissue toxicity was assessed from the beginning of FLASH-RT to 12-month post-irradiation. Results:A 1-year follow-up was achieved for scrotal lesions treated with electron FLASH-RT in patients with extramammary Paget disease. Electron FLASH-RT was safe, and treatment-related adverse events were mild. Transient skin toxicity occurred 2-5 weeks post FLASH-RT, and exudation and burning pain were significantly alleviated. A complete response was achieved 2-3 months post FLASH-RT, and the tumor lesions were covered by the normal epithelium of the scrotum. At the end of the one-year follow-up, the tumor lesions continued to respond, and one-year survival was achieved without additional injury to the irradiated areas after FLASH-RT. Conclusion:Fractionated electron FLASH-RT is feasible and safe for the treatment of extramammary Paget disease of the scrotum. Our findings support further exploration of electron FLASH-RT in patients with skin tumors.

Aims: Programmed death-1 (PD-1) blockade is a vital therapy for solid tumors, but not all patients benefit. Identifying which patients will benefit from immunotherapy is a key focus in oncology research. Patients & Methods: This study analyzed the correlation between the number of peripheral lymphocytes and the efficacy and prognosis of immunotherapy in advanced malignant melanoma. Results: Patients with a partial response had significantly lower peripheral B cell levels, and patients with a lower number of B lymphocytes had a longer survival time. Conclusion: These results suggest that peripheral B cells are correlated with the efficacy of PD-1 antibody and prognosis and are thus potential biomarkers for the efficacy and prognosis of PD-1 antibody immunotherapy in malignant melanoma.

Background Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. Methods This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. Discussion This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. Trial registration ChiCTR1800017646.

IntroductionThe management of soft tissue sarcomas presents considerable therapeutic challenges. This study was designed to assess the efficacy of neoadjuvant sequential chemotherapy and hypofractionated radiotherapy in conjunction with extensive surgical resection for the treatment of high-risk soft tissue sarcomas.Materials and methodsWe performed a retrospective review of 31 high-risk soft tissue sarcoma patients treated at our institution from June 2021 to June 2023. The cohort consisted of 21 males and 10 females with a mean age of 55.7 years and included both initial and recurrent disease presentations. Our treatment regimen comprised two to three cycles of neoadjuvant chemotherapy coupled with hypofractionated radiotherapy, delivered at 5 Gy per fraction to a total dose of 25–35 Gy across 5–7 days, prior to surgical resection aimed at achieving wide margins. Data collection was systematic, covering surgical outcomes, chemoradiotherapy-related complications, and prognostic factors.ResultsAll patients completed the prescribed course of neoadjuvant chemoradiotherapy. 29% patients experienced grade 3+ chemotherapy toxicity, necessitating a reduction or interruption in their chemotherapy regimen. Limb preservation was accomplished in 30 patients finally. Response evaluation using RECIST 1.1 criteria post-neoadjuvant therapy revealed 9.7% with PD, 58.1% with SD, 29% with a PR, and 3.2% with a CR, culminating in an ORR of 32.2%. Postoperative complications included superficial wound infections in four patients and deep incisional infections in another four. 6 patients had developed metastasis, and 3 patients were still alive. Two experienced local recurrence. One-year DFS was 79.3%, with a one-year OS rate of 89.6%.ConclusionNeoadjuvant sequential chemotherapy and hypofractionated radiotherapy followed by extensive surgical resection represents an effective treatment paradigm for high-risk soft tissue sarcomas. This multimodal approach not only facilitates tumor reduction but also significantly reduces the risks of local recurrence and distant metastasis.

Objective:To compare the radiation chemistry effects on water molecules after ultra-high dose rate (FLASH) and conventional irradiation.Methods:Both FLASH and conventional irradiation were applied to ultrapure water, with the hydroxyl radical yield in the homogeneous phase detected using electron paramagnetic resonance (EPR) and the hydrogen peroxide (H 2O 2) yield in the diffusion phase analyzed uuxing fluorescence probe. The liposome model was then established to investigate the radiation chemistry effect of FLASH and conventional irradiation in inducing lipid peroxidation. Results:Radiation chemistry reactions were observed in water molecules after irradiation. In the homogeneous phase, the yield of free radicals using FLASH irradiation is similar to those from conventional irradiation ( P>0.05). In the diffusion phase, the amount of H 2O 2 produced by FLASH irradiation was significantly lower than those from conventional irradiation ( t=0.49-12.81, P<0.05). The liposome model confirmed that conventional irradiation could significantly induce lipid peroxidation through the radiation chemistry effect in water molecules as compared with FLASH irradiation ( t=0.31-11.73, P<0.05). Conclusions:The radiation chemistry effect in water molecules after FLASH irradiation was significantly lower than that from conventional irradiation. This could be one of the mechanisms of FLASH effect.

Background: Tyrosine kinase inhibitors that act against epidermal growth factor receptor (EGFR) show strong efficacy against non-small cell lung cancer (NSCLC) involving mutated EGFRs. However, most such patients eventually develop resistance to EGFR-TKIs. Numerous researches have reported that messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) may be involved in EGFR-TKI resistance, but the comprehensive expression profile and competitive endogenous RNA (ceRNA) regulatory network between mRNAs and ncRNAs in EGFR-TKI resistance of NSCLC are incompletely known. We aimed to define a ceRNA regulatory network linking mRNAs and non-coding RNAs that may mediate this resistance.Methods: Using datasets GSE83666, GSE75309 and GSE103352 from the Gene Expression Omnibus, we identified long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs differentially expressed between NSCLC cells that were sensitive or resistant to EGFR-TKIs. The potential biological functions of the corresponding differentially expressed genes were analyzed based KEGG pathways. We combined interactions among lncRNAs, miRNAs and mRNAs in the RNAInter database with KEGG pathways to generate transcriptional regulatory ceRNA networks associated with NSCLC resistance to EGFR-TKIs. Kaplan-Meier analysis was used to assess the ability of core ceRNA regulatory sub-networks to predict the progression-free interval and overall survival of NSCLC. The expression of two core ceRNA regulatory sub-networks in NSCLC was validated by quantitative real-time PCR.Results: We identified 8,989 lncRNAs, 1,083 miRNAs and 3,191 mRNAs that were differentially expressed between patients who were sensitive or resistant to the inhibitors. These DEGs were linked to 968 biological processes and 31 KEGG pathways. Pearson analysis of correlations among the DEGs of lncRNAs, miRNAs and mRNAs identified 12 core ceRNA regulatory sub-networks associated with resistance to EGFR-TKIs. The two lncRNAs ABTB1 and NPTN with the hsa-miR-150–5p and mRNA SERPINE1 were significantly associated with resistance to EGFR-TKIs and survival in NSCLC. These lncRNAs and the miRNA were found to be down-regulated, and the mRNA up-regulated, in a resistant NSCLC cell line relative to the corresponding sensitive cells.Conclusion: In this study, we provide new insights into the pathogenesis of NSCLC and the emergence of resistance to EGFR-TKIs, based on a lncRNA-miRNA-mRNA network.

[This retracts the article DOI: 10.1016/j.omtn.2019.11.030.].

Majority Chinese esophageal cancer patients have squamous cell carcinoma (ESCC) and with metastasis at initial diagnosis. Treatment for metastatic ESCC where first-line chemotherapy failed is an unmet medical need. Targeting human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor 2 (KDR) have been approved to be effective for esophageal adenocarcinoma (EAC). We explored the clinical relevance of these molecular signaling in ESCC cohorts and collected clinical evidence on applying apatinib, a Chinese FDA-approved KDR inhibitor for late-stage gastric carcinoma, in 26 patients with chemotherapy-refractory metastatic ESCC. The clinical response rate and disease control rate of these patients to apatinib 500mg once daily regimen was 12% and 60%, respectively. The patients’ median progression-free survival time (PFS) was 3.2 months (95% CI, 2.23-4.17 months) and overall survival time (OS) was 5.3 months (95% CI, 4.46-6.14 months). The most common grade 3-4 treatment-related adverse events included leukopenia (7.7%) and anemia (7.7%). No drug-related death occurred. In conclusion, apatinib has favorable activity and acceptable safety, and could be a new treatment option for patients with chemotherapy refractory metastatic ESCC.

Esophageal cancer represents the eighth most frequently occurring cancer, as well as the sixth most widespread cause of cancer-related deaths. In recent years, accumulating evidence has implicated long non-coding RNAs in the progression of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the potential involvement and underlying mechanisms of LINC00337 in ESCC. Expression patterns of LINC00337 and targeting protein for Xenopus kinesin-like protein 2 (TPX2) in ESCC tissues and cells were detected using RT-qPCR and immunohistochemical staining. Next, the interactions among LINC00337, E2F4, and TPX2 were identified using chromatin immunoprecipitation, dual-luciferase reporter, and RNA-binding protein immunoprecipitation assays, suggesting that LINC00337 could recruit E2F4 to enhance the transcription of TPX2. Thereafter, the regulatory roles of LINC00337 and TPX2 in ESCC were analyzed by altering the expression of LINC00337 or TPX2 in ESCC cells following treatment with cisplatin (DDP). The levels of autophagy-related proteins Beclin1 and LC3II/LC3I, viability, autophagy, apoptosis, and chemoresistance of ESCC cells to DDP were measured following transfection treatment with different plasmids. Additionally, the role of the LINC00337/E2F4/TPX2 axis was assessed in vivo by measuring tumor formation in nude mice. The results demonstrated that LINC00337 upregulated TPX2, consequently leading to elevated levels of Beclin1 and LC3II/LC3I, promoted cell viability and autophagy, while inhibiting apoptosis and chemosensitivity to DDP in ESCC. In sum, the current study evidenced that the overexpression of LINC00337 could potentially enhance ESCC cell autophagy and chemoresistance to DDP via the upregulation of TPX2 by recruiting E2F4. Thus, LINC00337 may serve as a potential candidate for the treatment of ESCC.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is correlated to various malignant tumors. Consequently, we explored effects of lncRNA PVT1 on esophageal carcinoma (EC) targeting microRNA-145 (miR-145). EC tissues, adjacent normal tissues, and EC-related cell lines were collected and cultured. Expression of lncRNA PVT1, miR-145, fascin-1 (FSCN1), and related genes with intervening expression of PVT1 and miR-145 was determined. Bioinformatic website, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) were carried to verify target relationship among lncRNA PVT1, FSCN1, and miR-145. Scratch test, Transwell assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and flow cytometry were performed for detection of migration, invasion, viability, and apoptosis of transfected cells, respectively. Finally, tumor formation in nude mice was measured. After database analysis, lncRNA PVT1, miR-145, and FSCN1 were selected for study. lncRNA PVT1 and FSCN1 can bind to miR-145. After overexpressing miR-145 or inhibiting lncRNA PVT1, EC cell viability, migration, and invasion were inhibited, while volume and weight of tumor formation in nude mice decreased. Expression of IncRNA PVT1, FSCN1, Bcl-2, CD147, VEGFR2, and MTA1 decreased and expression of miR-145 and Box increased. Silencing lncRNA PVT1 can upregulate miR-145, which is a tumor suppressor in EC via knockdown of FSCN1. Thus, we might provide a potential theoretical basis for EC treatment.

The results indicate that KDR and VEGF are consistently over-expressed in multiple ESCC cohorts, while the expression of HER2 is even downregulated in ESCC, suggesting a potential anti-KDR strategy for ESCC.Apatinib was approved by Chinese FDA in 2014 for patients with latestage gastric carcinoma through targeting KDR.It has been reported to inhibit VEGF-mediated tumor microvascular density and tumor growth in ESCC cell lines and xenograft mice [5].Some patients with advanced EC have tried various targeted drugs as a subsequent line treatment including apatinib [6,7].However, most of the studies were not stratified according to tumor histology, a systematic study focusing on the efficacy and safety of apatinib for the ESCC patient with chemotherapy-refractory metastasis is barely reported.In this regard, we conducted a retrospective study and investigated the efficacy and toxicity of apatinib in treating 26 patients with chemotherapy-refractory metastatic ESCC. Methods Bioinformatics data miningGSE23400 dataset including 53 ESCC tumor samples and 53 adjacent paired normal esophagus samples [8] and GSE20347 dataset including 17 ESCC micro-dissected tumor samples and 17 matched samples from adjacent normal esophagus tissue [9] were used to analyze the mRNA expression and DNA copy number of HER2, KDR and VEGF in ESCC.GSE13898 dataset including 75 EAC samples from 64 patients and 28 paired normal esophageal samples [10] and

Objective To compare relevant dosimetric parameters of non-coplanar volumetric modulated arc therapy (VMAT) in treating brain tumors in conventional flattening filter (FF) or flattening filter-free (FFF) delivery mode,aiming to explore the appropriate evaluation method of accelerator for stereotactic radiosurgery (SRS).Methods Clinical data of 10 patients with single cranial tumor were retrospectively analyzed.All patients received non-coplanar VMAT at a prescription dose of 25 Gy in 1 fraction.Dosimetric parameters including conformity index (CI),heterogeneity index (HI),gradient index (GI50,GI25),gradient,volume of the brain tissue receiving larger than 10 Gy and 12 Gy (V10 and V12) and beam-on time were statistically compared between two treatment plans by paired sample t-test.Results When FFF-VMAT was compared with FF-VMAT in SRS for intracranial tumors,Paddick gradient index GI50 was 2.91±0.34 vs.3.07±0.35,6.91±0.28 vs.7.35±0.27 for GI25,(0.57±0.07) cm vs.(0.61±0.08) cm for gradient,respectively (all P＜0.05),whereas CI did not significantly differ (P＞0.05).For the normal brain tissues,the average dose was (160.64±43.64) cGy vs.(174.27± 53.98) cGy,(45.35± 30.32) ％ vs.(48.37± 30.88) ％ for V10 and (36.69±25.15) ％ vs.(39.48±25.37) ％ for V12,respectively (all P＜0.05).Conclusions Non-coplanar VMAT in FFF delivery mode can improve dose distribution and normal brain tissue sparing in the treatment of intracranial single tumors.Meanwhile,supplement of GI index and gradient index can implement comprehensive evaluation of the SRS planning.

Objective To explore the role of radiotherapy in the treatment of primary central nervous system lymphoma. Methods Clinical data of 60 patients diagnosed with primary central nervous system lymphoma from September 2010 to December 2017 were retrospectively analyzed. Among them, 50 cases were diagnosed by histopathological examination after stereotactic biopsy or tumor resection and 10 patients were diagnosed by gadolinium enhanced magnetic resonance imaging ( MRI) . Fifty-two patients underwent chemotherapy, and 45 of them received methotrexate-based chemotherapy, 25 received rituximab-based regimen. Twenty-seven patients were given with planned whole brain radiotherapy, while 33 patients were not. Salvage radiotherapy was delivered in 9 patients after treatment failure. Results The median follow-up time was 28 months ( 5-70 months) . The median overall survival time and median progression-free survival time of the whole patients was 22 months ( 5-65 months) and 13 months ( 5-55 months) , respectively. The 4-year overall survival rate and progression-free survival rate were 61% and 33%, respectively. The 4-year overall survival rates between patients with and without planned whole brain radiotherapy were 68% and 54% ( P=0.083) . The 4-year progression-free survival rates between patients with and without planned whole brain radiotherapy were 47% and 20% ( P=0.014) , respectively. Patients with and without salvage whole brain radiotherapy had a 4-year overall survival of 49% and 68%, respectively ( P=0.398) . Among patients who received whole brain radiotherapy, patients with a lower dose of ≤36 Gy had a similar overall survival compared with those with a higher dose of>36 Gy ( 80% vs. 45%, P=0.136) . Conclusions Radiotherapy is part of the comprehensive treatment of primary central nervous system lymphoma. Planned radiotherapy may bring clinical benefits to patients during the comprehensive therapy. However, the irradiation dose to the whole brain should not be too high because of neurotoxicity.

Cancer stem cells (CSCs) have been reported to be involved in esophageal cancer (EC) development. Hence, we aim to explore whether microRNA-135a (miR-135a) affects EC and its associated mechanism. Cancerous and adjacent tissues from 138 EC patients were collected. The dual-luciferase reporter gene assay and bioinformatics analysis were used to confirm the interaction between nucleotides. A series of mimics or inhibitors of miR-135a or small interfering RNA (siRNA) against Smo were introduced into EC cells. After that, the expression of miR-135a and Hedgehog (Hh) signaling pathway-related genes (Smo, Gli1, Shh, and Gli2) in tissues and cells was measured, accompanied by evaluation of cell viability, apoptosis, invasion, and migration. High expression of Smo, Gli1, Shh, and Gli2 and low expression of miR-135a were observed in EC. Smo was verified to be a target gene of miR-135a. In addition, overexpression of miR-135a or silencing of Smo decreased the expression of Gli1, Gli2, and Shh, thus inhibiting EC cell proliferation, migration, and invasion and promoting apoptosis. Silencing of miR-135a was observed to reverse the inhibitory role of miR-135a in EC. These results suggest that miR-135a inhibited the migration and invasion of EC cells through inhibition of the Smo/Hh axis.

Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) functions as a crucial regulator in the progression and development of human cancers. We analyzed effects of HAGLR, microRNA (miR)-143-5p and lysosome-associated membrane glycoprotein (LAMP)3 on esophageal cancer (EC) and the related mechanisms. Microarray analysis was used to screen out EC-related genes and the regulation network among HAGLR, miR-143-5p, and LAMP3. The regulatory mechanisms of HAGLR and miR-143-5p in EC were analyzed following the treatment of miR-143-5p mimic, miR-143-5p inhibitor, HAGLR vector, or small interfering RNA against HAGLR in EC cells. The expression of N-cadherin, vimentin, Twist1, Snail1, and E-cadherin as well as the abilities of cell proliferation, invasion, and migration were measured. The effects of the HAGLR/miR-143-5p/LAMP3 axis were determined in vivo by assessing tumor formation in nude mice. The expression of HAGLR and LAMP3 was increased, whereas that of miR-143-5p was diminished in EC tissues and cells. HAGLR could competitively bind to miR-143-5p, and miR-143-5p targeted LAMP3. Down-regulated HAGLR or up-regulated miR-143-5p increased E-cadherin expression and significantly diminished expression of LAMP3, N-cadherin, vimentin, Twist1, and Snail1. Moreover, down-regulated HAGLR inhibited cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and tumor growth. Moreover, down-regulation of HAGLR inhibited LAMP3 expression by sponging miR-143-5p, thereby suppressing the progression of EC. Taken together, our results suggest HAGLR acts as a competing endogenous RNA of miR-143-5p to increase the expression of LAMP3, thus promoting EMT, proliferation, invasion, and migration in EC cells.-Yang, C., Shen, S., Zheng, X., Ye, K., Sun, Y., Lu, Y., Ge, H. Long noncoding RNA HAGLR acts as a microRNA-143-5p sponge to regulate epithelial-mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3.