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丝氨酸 727 磷酸化是诱导食管鳞状细胞癌中 STAT3 介导的 LINC00184 转录所必需的。

Serine 727 phosphorylation is necessary to induce the STAT3-mediated transcription of LINC00184 in oesophageal squamous cell carcinoma.

机构信息

Department of Pathology, Henan No.3 Provincial People's Hospital, Zhengzhou, 450006, Henan, China.

Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

出版信息

Mol Cell Biochem. 2022 Jun;477(6):1775-1787. doi: 10.1007/s11010-022-04405-4. Epub 2022 Mar 21.

Abstract

LINC00184 has been suggested to be associated with cancer prognosis and has been implicated in cancer glycolysis; however, its role in oesophageal squamous cell carcinoma (ESCC) remains poorly understood. Herein, to understand the expression and the biological roles of LINC00184 in ESCC, in situ hybridization (ISH) and quantitative PCR (qPCR) were performed to detect the expression of LINC00184 in tissue blocks and in fresh tissues, respectively. Furthermore, with an in vitro cell culture system, LINC00184 was stably knocked down in ESCC cell lines KYSE-150 and Eca109, followed by determining alterations in their proliferation and motility relative to control. To gain insight into the regulation of LINC00184, STAT3 was bioinformatically identified as a transcription factor of LINC00184, which was further corroborated by chromatin-immunoprecipitation (CHIP) assay. The dephosphorylation of STAT3 with NSC74859 was shown to be unable to suppress the expression of LINC00184 in vivo in a xenograft mouse model. Moreover, STAT3, once phosphorylated at serine 727, tended to translocate into the mitochondria to promote LINC00184 expression in ESCC cells. Together, these data strongly support the oncogenic role of LINC00184 in ESCC.

摘要

LINC00184 被认为与癌症预后相关,并与癌症糖酵解有关;然而,其在食管鳞状细胞癌(ESCC)中的作用仍知之甚少。在此,为了了解 LINC00184 在 ESCC 中的表达和生物学作用,通过原位杂交(ISH)和定量 PCR(qPCR)分别检测组织块和新鲜组织中 LINC00184 的表达。此外,通过体外细胞培养系统,在 ESCC 细胞系 KYSE-150 和 Eca109 中稳定敲低 LINC00184,然后相对于对照确定其增殖和迁移的变化。为了深入了解 LINC00184 的调控机制,生物信息学鉴定 STAT3 是 LINC00184 的转录因子,染色质免疫沉淀(CHIP)实验进一步证实了这一点。用 NSC74859 使 STAT3 去磷酸化,在异种移植小鼠模型中不能抑制体内 LINC00184 的表达。此外,一旦 STAT3 丝氨酸 727 磷酸化,就倾向于易位到线粒体,以促进 ESCC 细胞中 LINC00184 的表达。总之,这些数据有力地支持了 LINC00184 在 ESCC 中的致癌作用。

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