Mechanism of Exosomal LncRNA PART1 in Esophageal Cancer Angiogenesis by Targeting miR-302a-3p/CDC25A Axis.

OBJECTIVE: LncRNA PART1 has been confirmed related to multiple cancer bioactivities mediated with vascular endothelial growth factor signaling. Nevertheless, the role of LncRNA PART1 in esophageal cancer induced angiogenesis remains unclear. The present work focused on assessing LncRNA PART1 effects on esophageal cancer-induced angiogenesis and exploring possible mechanisms. METHODS: Western blot and immunofluorescence were conducted for identifying EC9706 exosomes. MiR-302a-3p and LncRNA PART1 levels were assessed by real-time quantitative polymerase chain reaction. Cell Counting Kit-8, EdU, wound healing, transwell, and tubule information were adopted for detecting human umbilical vein endothelial cell viability, proliferation, migration, invasion, and tubule information, respectively. Starbase software and dual-luciferase reporter were conducted for predicting and judging the expression interrelation of LncRNA PART1 and its potential target-miR-302a-3p. The same methods were carried out for verifying the inhibiting influences of miR-302a-3p upregulation and its potential target-cell division cycle 25 A. RESULTS: LncRNA PART1 levels were upregulated and related to the overall survival of patients in esophageal cancer. EC9706-Exos accelerated human umbilical vein endothelial cell proliferation, migration, invasion, and tubule formation via LncRNA PART1. LncRNA PART1 served as a sponge of miR-302a-3p, then miR-302a-3p targeted cell division cycle 25 A, and EC9706-Exos accelerated human umbilical vein endothelial cell angiogenesis via LncRNA PART1/ miR-302a-3p/cell division cycle 25 A axis. CONCLUSION: EC9706-Exos accelerates human umbilical vein endothelial cell angiogenesis via LncRNA PART1/miR-302a-3p/ cell division cycle 25 A axis, indicating EC9706-Exos may act as a promoter of angiogenesis. Our research will contribute to clarify the mechanism of tumor angiogenesis.

Long-term outcomes in patients with central and ultracentral non-small cell lung cancer treated with stereotactic body radiotherapy: single-institution experience.

OBJECTIVE: Treatment-related toxicity following stereotactic ablative radiotherapy (SABR) in patients with central and ultracentral non-small cell lung cancer (NSCLC) is of potential concern, and the best regimens are still being explored. This study aimed to evaluate the clinical outcomes and toxicities of the patients with ultracentral and central NSCLC treated with SABR at our institution. METHOD: This retrospective study included patients with central and ultracentral NSCLC treated with SABR to prescription doses of 50 Gy in five fractions, 56 Gy in seven fractions, or 60 Gy in ten fractionsat Jiangsu Cancer Hospital between May 2013 and October 2018. The patients were grouped as central or ultracentral tumors.Overall survival (OS), progression-free survival (PFS), and grade ≥3 toxicities were analyzed. RESULTS: Forty patients (31 male, nine female) were included. Median follow-up was 41 (5-81) months. The 1-, 2-, and 3-year OS rates were 90.0%, 83.6%, and 66.0%, respectively, and the 1-, 2-, and 3-year PFS rates were 82.5%, 62.9%, and 54.2%, respectively. OS in the ultracentral group was inferior compared with the central group (median, 52.0 months, 95%CI: 43.0-61.0 vs. not reached, P=0.03).The median PFS was 38.0 months in the ultracentral group (95%CI: 19.8-56.2) vs. not reached in the central group, although this difference was not statistically significant (P= 0.06). The overall incidence of grade ≥3 toxicity was five (12.5%) patients, (5 in the ultracentralgroup vs. 0 in the central group; P=0. 11), including one patient with grade 3 pneumonitis, two with grade 3 bronchial obstruction, one with grade 5 bronchial obstruction, and one with grade 5 esophageal perforation. CONCLUSION: Worse outcomes were obseverd in patients with ultracentral NSCLC than those with central tumors after SABR. Higher rate of treatment-related grade 3 or more toxicity was observed in the ultracentral group.

Long non­coding RNA SNHG3 promotes the development of non­small cell lung cancer via the miR­1343­3p/NFIX pathway.

The aim of the present study was to identify the function of long non­coding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) and examine its effects on non­small cell lung cancer (NSCLC). A series of in vitro experiments were employed to evaluate the effects of SNHG3 on the progression of NSCLC, including Cell Counting Kit­8, 5­Ethynyl­2'­deoxyuridine, flow cytometry, wound healing, Transwell, western blotting and reverse transcription­quantitative PCR assays. Bioinformatics analyses and a luciferase reporter assay were performed to identify the target gene of SNHG3 and microRNA (miR)­1343­3p. Finally, recuse experiments were conducted to verify the effect of SNHG3 and its target gene on proliferation, apoptosis, migration and invasion. The findings indicated that lncRNA SNHG3 was highly expressed in NSCLC tissues and cell lines. Knockdown of lncRNA SNHG3 inhibited cell proliferation, migration and invasion, and accelerated cell apoptosis in NSCLC cell lines. The results of the bioinformatics analysis and the luciferase reporter assay indicated that lncRNA SNHG3 directly bound to miR­1343­3p and that it could downregulate the expression levels of miR­1343­3p to promote the progression of NSCLC. Rescue experiments indicated that lncRNA SNHG3 increased nuclear factor IX (NFIX) expression by sequestering miR­1343­3p in NSCLC. These results suggested that the SNHG3/miR­1343­3p/NFIX axis may serve as a novel prognostic biomarker and therapeutic target for NSCLC.

miR­378a­3p exerts tumor suppressive function on the tumorigenesis of esophageal squamous cell carcinoma by targeting Rab10.

Esophageal squamous cell carcinoma (ESCC) is a life­threatening cancer with increasing incidence worldwide. MicroRNAs (miRs) have been reported to be involved in the progression of various types of cancer. In previous studies, the expression of miR­378a­3p was shown to be reduced in ESCC tissues. However, the mechanism underlying the effect of miR­378a­3p in ESCC remains to be elucidated. By employing a reverse transcription­quantitative polymerase chain reaction, miR­378a­3p expression was tested in ESCC tissues and cell lines. In addition, the effects of miR­378a­3p on cell viability, proliferation, apoptosis, migration and invasion were studied using an MTT assay, an EdU assay, flow cytometry analysis, wound healing analysis and a Transwell assay. In the present study, the level of miR­378a­3p was significantly downregulated in ESCC clinical tissues and cell lines (EC109 and KYSE150). In addition, the overexpression of miR­378a­3p suppressed the viability, proliferation, migration and invasion of the ESCC cells. The upregulated expression of miR­378a­3p also increased the expression levels of B­cell lymphoma 2­associated X protein and caspase­3, and decreased the expression levels of matrix metalloproteinase (MMP)­2 and MMP­9, which attenuated ESCC tumorigenesis. Furthermore, Rab10 was confirmed to be a direct target gene of miR­378a­3p, and was negatively affected by miR­378a­3p. The silencing of Rab10 revealed antitumor effects in ESCC cell lines, and the expression of miR­378a­3p was negatively correlated with that of Rab10 in ESCC. Collectively, miR­378a­3p may act as a tumor­suppressor in ESCC cells through negatively regulating Rab10.

Salvage radiochemotherapy for lymph node recurrence after radical surgery of esophageal cancer.

To evaluate the efficacy of salvage radiochemotherapy (SRC) in patients with recurrent lymph node after radical surgery in esophageal cancer.This study enrolled 58 patients with esophageal squamous cell carcinoma who underwent SRC for lymph node recurrence after radical surgery from August 2011 to November 2015 at our hospital. Survival rates were calculated by the Kaplan-Meier method with the log-rank test. Multivariate analysis was conducted using the Cox model.The overall 1-, 3-, and 5-year survival rates after radical surgery were 94.8%, 53.0%, and 29.6%, respectively. The 1- and 3-year survival rates after SRC were 68.7% and 26.9%, respectively. The major acute toxicities were esophagitis and neutropenia, while most toxicities were grade 1 or 2. There was no unexpected increase in serious adverse events or treatment-related deaths. The results of multivariate analysis showed that time to recurrence (odds ratio [OR]: 0.25, 95% confidence interval [CI]: 0.11-0.53, P = .0004), T stage (OR: 2.75, 95%CI: 1.16-6.49, P = .021), and prophylactic radiotherapy/chemotherapy (PRC, OR: 0.39, 95%CI: 0.16-0.98, P = .045) were determinants of postoperative overall survival, and PRC was the only factor affecting the outcome of SRC (OR: 0.28, 95%CI: 0.12-0.70, P = .006).SRC is an effective treatment for recurrent lymph node after radical surgery of esophageal cancer.

Circulating tumor cells in the blood of poorly differentiated nasal squamous cell carcinoma patients: correlation with treatment response.

CONCLUSION: The results implied that CTCs were common even in early TNM stages and might become a potential parameter in evaluating therapeutic effects of radio and chemotherapies. BACKGROUND: Nasopharyngeal carcinoma (NPC) is a head and neck malignancy with an extraordinary high incidence in Southern China and a high metastasis rate. Analysis of circulating tumor cells (CTCs) in peripheral blood is a relatively new prognostic marker for cancer patients. PATIENTS AND METHODS: This retrospective study included data from 38 nasopharyngeal patients with poorly differentiated squamous cell carcinoma in TNM stage I (n = 2), TNM stage II (n = 12), TNM stage III (n = 8), and TNM stage IV (n = 16). CTCs in peripheral blood of all patients were counted before and 1 week as well as 1 months after radiotherapy. RESULTS: The data showed that in 52.6% of the patients CTCs could be detected in peripheral blood and the numbers were significantly decreased 1 month after radiotherapy treatment (p < 0.001). There was no correlation between CTC number or positivity and TNM stages or other clinical parameters.