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LINC01535 通过激活 JAK/STAT3 通路促进食管鳞癌细胞增殖并抑制细胞凋亡。

LINC01535 promotes proliferation and inhibits apoptosis in esophageal squamous cell cancer by activating the JAK/STAT3 pathway.

机构信息

Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3694-3700. doi: 10.26355/eurrev_202004_20832.

Abstract

OBJECTIVE

To detect the expression of long intergenic non-coding ribonucleic acid (LINC) 01535 in esophageal squamous cell cancer (ESCC) tissues and cells, and to investigate the influences of LINC01535 on the proliferation and apoptosis of ESCC cells and the possible mechanism.

PATIENTS AND METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of LINC01535 in 43 cases of ESCC tissues and human esophageal cancer cells (KYSE30, EC9706, TE-13, and Ecal09) compared with human esophageal mucosal epithelial cells (HET-1A). The esophageal cancer cells with the highest expression were selected and transfected with small interfering RNA (si)-LINC01535 (experimental group) or si-negative control (NC) (control group). The interference efficiency was measured via qRT-PCR assay. Regulatory effects of LINC01535 on cell proliferative capacity was examined through colony formation assay and cell proliferation assay [Cell Counting Kit-8 (CCK-8)]. Cell cycle and apoptosis influenced by LINC01535 were detected via flow cytometry. Western blotting was applied to determine the expression changes in the molecular markers of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway.

RESULTS

LINC01535 expression in ESCC tissues and cells was remarkably higher than that in para-carcinoma tissues and esophageal mucosal epithelial cells. Knockdown of LINC01535 decreased proliferative capacity, arrested cell cycle in G1/G0 phase, and increased apoptotic rate of ESCC cells. The expressions of the molecular markers of the JAK/STAT3 signaling pathway were altered after knockdown of LINC01535. The above results illustrated that LINC01535 accelerated the proliferation but repressed the apoptosis of ESCC cells by regulating the JAK/STAT3 signaling pathway.

CONCLUSIONS

The expression of LINC01535 is up-regulated in ESCC tissues and cells, and the highly expressed LINC01535 promotes the proliferation and inhibits the apoptosis of ESCC cells by regulating the JAK/STAT3 signaling pathway. Our findings provide new directions for the diagnosis and treatment of esophageal cancer.

摘要

目的

检测长链非编码 RNA(LINC)01535 在食管鳞状细胞癌(ESCC)组织和细胞中的表达,探讨 LINC01535 对 ESCC 细胞增殖和凋亡的影响及其可能的机制。

患者与方法

采用实时定量聚合酶链反应(qRT-PCR)检测 43 例 ESCC 组织和人食管癌细胞(KYSE30、EC9706、TE-13 和 Ecal09)与正常人食管黏膜上皮细胞(HET-1A)中 LINC01535 的相对表达。选择表达最高的食管癌细胞,转染小干扰 RNA(si)-LINC01535(实验组)或 si 阴性对照(NC)(对照组)。通过 qRT-PCR 检测干扰效率。通过集落形成实验和细胞增殖实验[细胞计数试剂盒-8(CCK-8)]检测 LINC01535 对细胞增殖能力的调节作用。通过流式细胞术检测 LINC01535 对细胞周期和凋亡的影响。Western blot 检测 Janus 激酶/信号转导和转录激活因子 3(JAK/STAT3)信号通路中分子标志物的表达变化。

结果

LINC01535 在 ESCC 组织和细胞中的表达明显高于癌旁组织和食管黏膜上皮细胞。LINC01535 敲低降低了 ESCC 细胞的增殖能力,使细胞周期停滞在 G1/G0 期,并增加了细胞凋亡率。LINC01535 敲低后 JAK/STAT3 信号通路的分子标志物表达发生改变。以上结果表明,LINC01535 通过调节 JAK/STAT3 信号通路加速 ESCC 细胞的增殖,抑制其凋亡。

结论

LINC01535 在 ESCC 组织和细胞中呈高表达,高表达的 LINC01535 通过调节 JAK/STAT3 信号通路促进 ESCC 细胞的增殖,抑制其凋亡。本研究为食管癌的诊断和治疗提供了新的方向。

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