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Long Non-coding RNA MIAT Mediates Non-small Cell Lung Cancer Development Through Regulating the miR-128-3p/PELI3 Axis.

长链非编码 RNA MIAT 通过调控 miR-128-3p/PELI3 轴介导非小细胞肺癌的发生发展。

  • 影响因子:1.60
  • DOI:10.1007/s10528-020-09979-6
  • 作者列表:"Li F","Li H","Li S","Lv B","Shi J","Yan H","Zhang H","He Y
  • 发表时间:2020-06-16
Abstract

:In this study, we set out to characterize the expression status of long non-coding RNA (lncRNA) Myocardial Infarction Associated Transcript (MIAT) in non-small cell lung cancer (NSCLC) and elucidate its mechanistic contribution to this disease. Relative expression levels of MIAT, Pellino E3 Ubiquitin Protein Ligase Family Member 3 (PELI3), and microRNA (miR)-128-3p were analyzed by real-time polymerase chain reaction. PELI3 protein level was determined by immunoblotting. Cell viability and proliferation were evaluated by the MTT assay and colony formation assay, respectively. Cell invasion and migration were assessed by wound-healing closure and transwell assays, respectively. The regulatory actions of miR-128-3p on both MIAT and PELI3 were interrogated by luciferase reporter assay. We demonstrated the aberrant upregulation of MIAT in NSCLC and its association with tumor progression. We further uncovered the negative correlation among MIAT, PELI3, and miR-128-3p. MIAT deficiency significantly compromised cell viability, proliferation, invasion, and migration, while increased miR-128-3p and decreased PELI3 expressions. Application of miR-128-3p inhibitor significantly stimulated luciferase activities driven by both MIAT and PELI3 promoter and phenotypically promoted cell viability, proliferation, migration, and invasion. Our study highlighted the mechanistic contribution of the MIAT/miR-128-3p/PELI3 signaling cascade in NSCLC.

摘要

: 在这项研究中,我们开始描述非小细胞肺癌 (NSCLC) 中长链非编码 RNA (lncRNA) 心肌梗死相关转录本 (MIAT) 的表达状态并阐明其对该疾病的机制贡献。通过实时聚合酶链反应分析 MIAT 、 Pellino E3 泛素蛋白连接酶家族成员 3 (PELI3) 和 microRNA (miR)-128-3p 的相对表达水平。通过免疫印迹法测定 PELI3 蛋白水平。分别用 MTT 法和集落形成法评价细胞活力和增殖。分别通过伤口愈合闭合和 transwell 试验评估细胞侵袭和迁移。通过荧光素酶报告基因检测询问 miR-128-3p 对 MIAT 和 PELI3 的调节作用。我们证明了 MIAT 在 NSCLC 中的异常上调及其与肿瘤进展的相关性。我们进一步揭示了 MIAT 、 PELI3 和 miR-128-3p 之间的负相关。MIAT 缺陷显著损害细胞活力、增殖、侵袭和迁移,同时增加 miR-128-3p,降低 PELI3 表达。应用 miR-128-3p 抑制剂显著刺激由 MIAT 和 PELI3 启动子驱动的荧光素酶活性,表型促进细胞活力、增殖、迁移和侵袭。我们的研究强调了 MIAT/miR-128-3p/PELI3 信号级联在 NSCLC 中的机制贡献。

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发表时间:2020-01-01
DOI:10.1016/j.asjsur.2019.03.008
作者列表:["Esme H","Can A","Şehitogullari A"]

METHODS:BACKGROUND:The objectives of this study are to assess the chest drainage volumes of patients undergoing anatomic resection of non-small cell lung carcinoma and to determine the safety and effectiveness of administering enoxaparin for thromboprophylaxis. METHODS:A total of 77 patients were included in the study. A study was conducted on the first group of 42 patients in which enoxaparin prophylaxis (enoxaparin, 40 mg) was subcutaneously injected once a day for a period of three days after the patients underwent anatomic pulmonary resection between March 2016 and March 2018. An enoxaparin-free group was identified and included 35 patients who received no enoxaparin prophylaxis after undergoing anatomic pulmonary resection between February 2013 and February 2016. We compared the changes in hemoglobin (Hb) levels, postoperative 3-day drainage volume, transfusion volume, pulmonary complications and length of stay between the two groups. RESULTS:No differences in postoperative Hb levels, chest drainage volume, transfusion volume, postoperative complications, and length of stay were observed between the two groups. Deep-vein thrombosis was noted in a patient in the enoxaparin-free group. No major bleeding was noted in either group. CONCLUSION:We found that for patients undergoing anatomic resection of primary lung cancer, the blood transfusion and chest drainage volumes did not differ, regardless of whether the patients were given enoxaparin. To the best of our knowledge, the impact of low-molecular-weight heparin on chest tube drainage volume for patients undergoing anatomic resection of non-small cell lung carcinoma has not been investigated before.

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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影响因子:8.44
发表时间:2020-02-01
DOI:10.1016/j.annonc.2019.10.022
作者列表:["Mazieres J","Cropet C","Montané L","Barlesi F","Souquet PJ","Quantin X","Dubos-Arvis C","Otto J","Favier L","Avrillon V","Cadranel J","Moro-Sibilot D","Monnet I","Westeel V","Le Treut J","Brain E","Trédaniel J","Jaffro M","Collot S","Ferretti GR","Tiffon C","Mahier-Ait Oukhatar C","Blay JY"]

METHODS:BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS:Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS:Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION:Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02304809.

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