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首页> 外文期刊>Oncology reports >Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway
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Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway

机译：长期非编码RNA Bancr通过RAF / MEK / ERK信号通路调节乳头状甲状腺癌中的癌症干细胞标志物

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摘要

Thyroid cancer is one of the most common malignant tumors of the endocrine system. Among all thyroid cancers, papillary thyroid carcinoma (PTC) is the most common type. The BRAF-activated non-coding RNA (BANCR) is a 693-bp nucleotide transcript which was first identified in melanoma. However, the role of BANCR in the development of thyroid cancer remains unclear. Therefore, the present study investigated the potential involvement of BANCR in the development of thyroid cancer in vitro using patient tissue samples and a panel of thyroid cancer cell lines, and in vivo using a xenograft mouse model. We observed that BANCR was expressed at a higher level in human thyroid tumor tissues than that noted in the adjacent normal tissues. The expression level of BANCR differed between cultured thyroid cancer cell lines; BANCR expression was lower in the BCPAP cell line than that observed in the CAL-62, WRO and FTC-133 cell lines. Western blot analysis and flow cytometry revealed that overexpression of BANCR in the BCPAP cell line resulted in increased expression of the cancer stem cell markers, LGR5 and EpCAM. Single-clone formation experiments showed that upregulated expression of BANCR in the BCPAP cell line promoted an increase in the number of clones formed. Similarly, in microsphere formation experiments, overexpression of BANCR resulted in increased number and size of microspheres compared with the control cell line. Western blotting experiments showed that BANCR overexpression in BCPAP upregulated the expression of phosphorylated c-Raf, MEK1/2 and ERK1/2. Inhibition of c-Raf via U0126 decreased the expression of LGR5 and EpCAM, as well as phosphorylated levels of c-Raf, MEK1/2 and ERK1/2 in the BCPAP cells, compared to levels in the DMSO controls. In the xenograft mouse model, BANCR overexpression in the thyroid cancer cells significantly increased tumor growth. Taken together, these results suggest that BANCR plays a role in PTC development by regulating the expression of cancer stem cell markers LGR5 and EpCAM via the c-Raf/MEK/ERK signaling pathway. Therefore, BANCR may be used as a novel prognostic marker for PTC.
机译：甲状腺癌是内分泌系统最常见的恶性肿瘤之一。在所有甲状腺癌中，乳头状甲状腺癌（PTC）是最常见的类型。 BRAF激活的非编码RNA（BANCR）是693bp核苷酸转录物，其首先在黑色素瘤中鉴定。然而，班克在甲状腺癌发展中的作用仍不清楚。因此，本研究调查了使用患者组织样品和甲状腺癌细胞系和使用异种移植小鼠模型的患者组织样品和甲状腺癌细胞系的体外潜在参与培训癌的潜在参与。我们观察到班克在人甲状腺肿瘤组织中的较高水平表达，而不是在相邻的正常组织中注意到。培养的甲状腺癌细胞系之间的表达水平不同; BCPAP细胞系箱表达低于CAL-62，WRO和FTC-133细胞系观察的细胞系。 Western印迹分析和流式细胞仪发现，BCPAP细胞系中箱的过度表达导致癌症干细胞标志物，LGR5和EPCAM的表达增加。单克隆形成实验表明，BCPAP细胞系中的上调表达在BCPAP细胞系中促进了形成的克隆数量。类似地，在微球形成实验中，与对照细胞系相比，箱的过表达导致微球的数量和大小增加。 Western Blotting实验表明，BCPAP中的班票过表达上调了磷酸化C-RAF，MEK1 / 2和ERK1 / 2的表达。通过U0126抑制C-RAF降低了LGR5和EPCAM的表达，以及BCPAP细胞中的C-RAF，MEK1 / 2和ERK1 / 2的磷酸化水平，与DMSO对照中的水平相比。在异种移植小鼠模型中，甲状腺癌细胞中的班克过表达显着增加了肿瘤生长。这些结果表明，班克通过通过C-RAF / MEK / ERK信号通路调节癌症干细胞标记物LGR5和EPCAM的表达，在PTC开发中发挥作用。因此，班克可以用作PTC的新型预后标志物。

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  • 来源
    《Oncology reports》 |2018年第2期|共8页
  • 作者

    Wang Yuanyuan; Lin Xiangde; Fu Xinghao; Yan Wei; Lin Fusheng; Kuang Penghao; Luo Yezhe; Lin Ende; Hong Xiaoquan; Wu Guoyang;

  • 作者单位

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

    Xiamen Univ Zhongshan Hosp Dept Gen Surg 201 Hubin Rd Xiamen 361004 Fujian Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

    PTC; BANCR; stem cell; LGR5; EPCAM; Raf-MEK-Erk;

    机译：PTC;班克;干细胞;LGR5;EPCAM;RAF-MEK-ERK;

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