CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma
CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma
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CDKN3通过激活AKT信号通路促进食管鳞癌细胞增殖、侵袭和迁移
DOI：
10.3892/ol.2019.11077
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发表时间：
2020-01-01
期刊：
影响因子：
2.9
通讯作者：
Yin, Li
中科院分区：
文献类型：
--
作者：
Yu, Hanxu;Yao, Jun;Yin, Li
在中国，食管鳞状细胞癌（ESCC）具有直接侵袭和早期转移的特点，死亡率很高。迫切需要确定驱动 ESCC 进展的分子基础并开发新的诊断生物标志物。细胞周期蛋白依赖性激酶抑制剂 3 (CDKN3) 在肿瘤发展的调节中发挥着至关重要的作用。本研究旨在探讨CDKN3在调节ESCC细胞增殖和侵袭中的功能和潜在机制。通过逆转录定量PCR评估ESCC细胞中CDKN3的表达水平。使用细胞计数试剂盒 8 和集落形成测定来评估细胞活力。进行伤口愈合测定以探索细胞迁移。进行Transwell侵袭分析来研究ESCC细胞的侵袭能力。通过蛋白质印迹测定检测蛋白质水平。结果表明，ESCC 组织中 CDKN3 的表达显着上调，正如使用 UALCAN 和 Gene Expression Omnibus 数据库预测的那样。 PCR 和蛋白质印迹测定证实 CDKN3 在 ESCC 细胞系中上调。功能分析显示，用小干扰RNA敲低CDKN3可降低ESCC细胞增殖、侵袭和迁移的能力，并抑制G1/S转变。进一步的机制分析表明，CDKN3通过激活ESCC细胞中的AKT信号通路来促进细胞增殖和侵袭。据我们所知，本研究首次确定了 CDKN3 在 ESCC 中的功能，并提供了 CDKN3 通过激活 AKT 信号通路调节肿瘤进展的证据。因此，CDKN3可能作为ESCC治疗的潜在有效治疗靶点。
In China, esophageal squamous cell carcinoma (ESCC), capable of direct invasion and early metastasis, exhibits high mortality. Identification of the molecular basis driving ESCC progression and development of new diagnostic biomarkers are urgently needed. Cyclin-dependent kinase inhibitor 3 (CDKN3) performs crucial roles in the modulation of tumor development. The present study aimed to explore the functions and underlying mechanism of CDKN3 in regulating ESCC cell proliferation and invasion. The expression levels of CDKN3 in ESCC cells were evaluated by reverse transcription-quantitative PCR. Cell counting kit-8 and colony forming assays were used to evaluate cell viability. Wound-healing assay was performed to explore cell migration. Transwell invasion analysis was conducted to investigate the invasive capacity of ESCC cells. Protein levels were detected by western blot assay. The results demonstrated that the expression of CDKN3 was significantly upregulated in ESCC tissues, as predicted using the UALCAN and Gene Expression Omnibus databases. PCR and western blot assays confirmed that CDKN3 was upregulated in ESCC cell lines. Functional assays revealed that CDKN3 knockdown with small interfering RNA decreased the ability of ESCC cells to proliferate, invade and migrate and suppressed G1/S transition. Further mechanistic analyses demonstrated that CDKN3 promoted cell proliferation and invasion by activating the AKT signaling pathway in ESCC cells. To the best of our knowledge, the present study is the first to identify the functions of CDKN3 in ESCC and provide evidence that CDKN3 regulates tumor progression by activating the AKT signaling pathway. Therefore, CDKN3 may serve as a potential effective therapeutic target for ESCC treatment.