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miR-1225-5p Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox9.

MiR-1225-5p通过靶向sox9 在骨肉瘤中起肿瘤抑制因子的作用。

  • 影响因子:2.78
  • DOI:10.1089/dna.2019.5105
  • 作者列表:"Zhang W","Wei L","Sheng W","Kang B","Wang D","Zeng H
  • 发表时间:2020-01-01

:microRNA plays an important role in the development of tumors, including osteosarcoma. However, the role of miR-1225-5p in osteosarcoma is currently unclear. First, we found that miR-1225-5p was downregulated in osteosarcoma cells relative to its levels in normal bone tissue by analyzing GSE28423 data in the GEO database. Using GSE39040, we found that low miR-1225-5p expression is associated with poor prognosis in patients with osteosarcoma, and we also found low miR-1225-5p expression in patients with recurrent osteosarcoma. We later demonstrated that osteosarcoma cell lines transfected with miR-1225-5p mimic had decreased ability to proliferate, migrate, and invade relative to control cells. To elucidate the mechanism by which miR-1225-5p inhibits the development of osteosarcoma, we identified Sox9 as a target gene of miR-1225-5p using the TargetScan website. We confirmed that Sox9 is the target gene of miR-1225-5p using the luciferase reporter assay. We then found that Sox9 is highly expressed in osteosarcoma by analyzing the GSE16088 and GSE42352 datasets and that high expression of Sox9 is associated with poor prognosis in patients with osteosarcoma using the R2 database. Further analysis using the TARGET database uncovered that high Sox9 expression is associated with a high recurrence rate in patients with osteosarcoma. Transfection of Sox9 siRNA inhibited the proliferation, migration, and invasiveness of osteosarcoma cells. We transfected miR-1225-5p together with Sox9 siRNA into osteosarcoma cells, observing strong inhibition of proliferation, migration, and invasiveness. Finally, exogenous expression of Sox9 partially reversed the anticancer effects of miR-1225-5p in osteosarcoma cells. Taken together, our findings suggest that miR-1225-5p functions as a tumor suppressor in osteosarcoma by targeting Sox9, thereby revealing new therapeutic targets for osteosarcoma.


: MicroRNA在肿瘤,包括骨肉瘤的发展中起重要作用。然而,miR-1225-5p在骨肉瘤中的作用目前尚不清楚。首先,我们通过分析GEO数据库中的GSE28423 数据,发现骨肉瘤细胞中miR-1225-5p相对于其在正常骨组织中的水平下调。使用GSE39040,我们发现低miR-1225-5p表达与骨肉瘤患者的不良预后相关,并且我们还在复发骨肉瘤患者中发现低miR-1225-5p表达。我们后来证明,与对照细胞相比,转染miR-1225-5p模拟物的骨肉瘤细胞系增殖、迁移和侵袭能力下降。为了阐明miR-1225-5p抑制骨肉瘤发展的机制,我们使用TargetScan网站确定Sox9 是miR-1225-5p的靶基因。我们通过荧光素酶报告基因检测证实Sox9 是miR-1225-5p的靶基因。然后我们通过分析GSE16088 和GSE42352 数据集发现Sox9 在骨肉瘤中高表达,并且使用R2 数据库发现Sox9 的高表达与骨肉瘤患者的不良预后相关。使用目标数据库的进一步分析发现,Sox9 高表达与骨肉瘤患者的高复发率相关。转染Sox9 siRNA可抑制骨肉瘤细胞的增殖、迁移和侵袭能力。我们将miR-1225-5p与Sox9 siRNA一起转染骨肉瘤细胞,观察到强烈的增殖、迁移和侵袭抑制。最后,Sox9 的外源性表达部分逆转了miR-1225-5p在骨肉瘤细胞中的抗癌作用。总之,我们的研究结果表明,miR-1225-5p通过靶向Sox9 在骨肉瘤中发挥肿瘤抑制因子的作用,从而揭示骨肉瘤新的治疗靶点。

关键词: Sox9 MiR-1225-5p 骨肉瘤


作者列表:["Tran S","Puric E","Walser M","Poel R","Datta NR","Heuberger J","Pica A","Marder D","Lomax N","Bolsi A","Morach P","Bachtiary B","Seddon BM","Schneider R","Bodis S","Weber DC"]

METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.

关键词: 暂无
翻译标题与摘要 下载文献
作者列表:["Gyori DJ","Bullington SM","Crawford BS","Vernon VP"]

METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.

翻译标题与摘要 下载文献
作者列表:["Dohzono S","Sasaoka R","Takamatsu K","Hoshino M","Nakamura H"]

METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.

翻译标题与摘要 下载文献