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miR-196b 是人类喉鳞状细胞癌的预后因素,通过靶向 SOCS2 促进肿瘤进展。

miR-196b is a prognostic factor of human laryngeal squamous cell carcinoma and promotes tumor progression by targeting SOCS2.

机构信息

Department of Otorhinolaryngology, Shengjing Hospital, China Medical University, Shenyang, China.

Department of Endocrinology Shengjing Hospital, China Medical University, Shenyang, China.

出版信息

Biochem Biophys Res Commun. 2018 Jun 22;501(2):584-592. doi: 10.1016/j.bbrc.2018.05.052.

Abstract

BACKGROUND

Laryngeal squamous cell carcinoma (LSCC) has the second highest incidence among the head and neck malignancies. Additionally, the incidence of LSCCs has been recently increasing. Therefore, understanding the mechanisms of LSCC tumorigenesis and identifying novel biomarkers to accurately predict and improve the prognosis of patients with LSCC is extremely important.

METHODS

miR-196b and SOCS2 expression was measured by qRT-PCR and western blot. Their correlation was analyzed with the Pearson test. TU212 and TU177 cells were cultured and transfected for MTT, Transwell, and apoptosis assays upon miR-196b knockdown, SOSC2 overexpression or SOCS2 silencing. Dual-luciferase reporter assay were conducted to identify the relationship between miR-196b and SOCS2. Moreover, the correlation between clinicopathological parameters and miR-196b/SOCS2 expression in patients was analyzed. Univariate and multivariate analysis and log-rank tests were used to determine if miR-196 was an independent LSCC prognostic factors.

RESULTS

We reported the aberrant expression and inverse correlation of miR-196b and SOCS2 in LSCC samples. miR-196b promoted LSCC cells proliferation and invasion, and suppressed apoptosis by directly inhibiting SOCS2 expression in vitro. Moreover, we also revealed that miR-196b/SOCS2 expression correlated with T stage and cervical metastasis. miR-196b was demonstrated to be an independent prognostic factor for overall survival of patients with LSCC.

CONCLUSIONS

Overexpression of miR-196b suppresses SOCS2 in human LSCC resulting in tumor progression and poor prognosis. miR-196b is a potential marker for prognosis assessment and targeting miR-196b may be a novel valuable strategy for the treatment of LSCC.

摘要

背景

喉鳞状细胞癌(LSCC)是头颈部恶性肿瘤中发病率第二高的肿瘤。此外,LSCC 的发病率最近一直在上升。因此,了解 LSCC 肿瘤发生的机制,寻找新的生物标志物来准确预测和改善 LSCC 患者的预后非常重要。

方法

通过 qRT-PCR 和 Western blot 检测 miR-196b 和 SOCS2 的表达。采用 Pearson 检验分析它们之间的相关性。在 TU212 和 TU177 细胞中敲低 miR-196b、过表达 SOCS2 或沉默 SOCS2 后进行 MTT、Transwell 和凋亡实验。通过双荧光素酶报告基因实验确定 miR-196b 与 SOCS2 之间的关系。此外,还分析了患者临床病理参数与 miR-196b/SOCS2 表达的相关性。采用单因素和多因素分析及对数秩检验确定 miR-196 是否为 LSCC 的独立预后因素。

结果

我们报道了 miR-196b 和 SOCS2 在 LSCC 样本中的异常表达和负相关。miR-196b 在体外通过直接抑制 SOCS2 的表达促进 LSCC 细胞的增殖和侵袭,抑制凋亡。此外,我们还发现 miR-196b/SOCS2 的表达与 T 分期和颈转移相关。miR-196b 是 LSCC 患者总生存期的独立预后因素。

结论

miR-196b 在人 LSCC 中高表达,抑制 SOCS2 的表达,导致肿瘤进展和预后不良。miR-196b 可能是一种潜在的预后评估标志物,靶向 miR-196b 可能是治疗 LSCC 的一种新的有价值策略。

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