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Overexpression of miR -155 Promotes Proliferation and Invasion of Human Laryngeal Squamous Cell Carcinoma via Targeting SOCS1 and STAT3

机译:miR -155的过表达通过靶向SOCS1和STAT3促进人喉鳞状细胞癌的增殖和侵袭

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摘要

MicroRNA155 plays an important role in many solid malignancies. Expression and function of miR-155 in laryngeal carcinoma have not been fully understood. This study aims to investigate the expression and function of miR-155 in laryngeal squamous cell carcinoma (LSCC), the relationship between miR-155 and its downstream target suppressor of cytokine signaling 1 (SOCS1)-STAT3 pathway, and the related clinicopathological factors. Sixty-three samples of laryngeal squamous cell carcinoma and twenty-one samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and real-time PCR. Hep-2 cells were cultured and transfected with miR-155 mimic and ASO. Cell proliferation, migration and invasion assays were used to determine the role of miR-155 in regulation of LSCC growth, migration, and invasion, respectively. The expression levels of miR-155 in LSCC were significantly higher than those in the control mucosa tissues. Downregulation of SOCS1 expression and elevated expression of STAT3 were also observed in LSCC. The relevance of the three factors were statistically significant. Moreover, knockdown of miR-155 elevated SOCS1expression level, suppressed STAT3 expression, and inhibited hep-2 cells growth, migration and invasion. Whereas overexpression of miR-155 inhibited SOCS1expression, elevated STAT3 expression, and promoted hep-2 cells growth, migration and invasion. Furthermore, the miR-155 levels in T3 T4 stages, and poor/moderate cell differentiation were significantly higher than those in T2 stage and higher degree of cell differentiation. The STAT3 protein in poor/moderate cell differentiation was significantly higher than those in higher degree of cell differentiation. We firstly demonstrated the aberrant expression and function of miR-155 and itsdownstream targets in LSCC. The current findings suggest that miR-155 play promotingrole during the development of LSCC, and miR-155 may be a useful marker for the prognosis and assessment of therapeutic effects.
机译:MicroRNA155在许多实体恶性肿瘤中起着重要作用。尚未完全了解miR-155在喉癌中的表达和功能。本研究旨在探讨miR-155在喉鳞状细胞癌(LSCC)中的表达和功能,miR-155及其下游细胞因子信号传导抑制因子1(SOCS1)-STAT3通路的抑制因子之间的关系以及相关的临床病理因素。使用蛋白质印迹分析和实时荧光定量PCR对从喉总切除病例中获得的63份喉鳞状细胞癌样本和21份对照黏膜样本进行了分析。培养Hep-2细胞,并用miR-155模拟物和ASO转染。细胞增殖,迁移和侵袭试验分别用于确定miR-155在LSCC生长,迁移和侵袭调节中的作用。 LSCC中miR-155的表达水平明显高于对照黏膜组织。在LSCC中也观察到SOCS1表达下调和STAT3表达升高。这三个因素的相关性具有统计学意义。而且,敲低miR-155可以提高SOCS1表达水平,抑制STAT3表达,并抑制hep-2细胞的生长,迁移和侵袭。而miR-155的过表达抑制SOCS1的表达,STAT3的表达升高并促进hep-2细胞的生长,迁移和侵袭。此外,在T3 T4期的miR-155水平以及差/中度细胞分化显着高于T2期和更高程度的细胞分化。 STAT3蛋白在细胞分化不良/中度时明显高于那些在较高细胞分化度中的蛋白质。我们首先证明了miR-155及其下游靶标在LSCC中的异常表达和功能。目前的发现表明,miR-155在LSCC的发展过程中起促进作用,而miR-155可能是预后和评估治疗效果的有用标志。

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