miR-22/KAT6B axis is a chemotherapeutic determiner via regulation of PI3k-Akt-NF-kB pathway in tongue squamous cell carcinoma.
miR-22/KAT6B axis is a chemotherapeutic determiner via regulation of PI3k-Akt-NF-kB pathway in tongue squamous cell carcinoma.
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miR-22/KAT6B 轴是舌鳞状细胞癌中通过调节 PI3k-Akt-NF-kB 通路的化疗决定因素
DOI：
10.1186/s13046-018-0834-z
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发表时间：
2018-07-24
期刊：
影响因子：
--
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Gu Y;Liu H;Kong F;Ye J;Jia X;Zhang Z;Li N;Yin J;Zheng G;He Z
舌鳞状细胞癌（TSCC）是最常见的口腔癌。晚期TSCC手术前后的新辅助全身治疗被认为是降低死亡率的最关键因素之一。然而，化疗的治疗益处通常由于内在和/或获得性耐药性而减弱，并且大部分TSCC对化疗具有耐药性，这可能导致更具侵袭性的肿瘤行为和甚至更差的临床结果。最近，使用miRNA来预测对癌症治疗的治疗反应的潜在应用具有很高的希望，但具有预测价值的miRNA仍有待确定，其潜在机制仍有待了解在TSCC.MethodsThe miR-22的表达在TSCC患者的组织中被诊断为TSCC使用实时PCR分析。通过MTS法和流式细胞术分析miR-22对TSCC细胞增殖和成瘤的影响。在异种移植模型中观察体内肿瘤生长。采用荧光素酶报告基因检测、实时荧光定量PCR和Western blot方法验证miR-22在TC中的潜在靶点。miR-22表达与KAT 6 B表达之间的相关性，以及miR-22调节PI 3 k-Akt-NF-kB通路的机制也被addressed.ResultsWe发现miR-22表达与TSCC患者对顺铂（CDDP）的化疗敏感性之间有很强的相关性。在体外和体内进行的实验模型中，miR-22的异位过表达增强了TSCC细胞对CDDP的凋亡反应。此外，我们发现KAT 6 B是miR-22的直接功能靶标。KAT 6 B的异位表达减弱了CDDP处理后TSCC细胞中miR-22的效率。miR-22过表达或KAT 6 B敲低可能通过下调PI 3 K/Akt/NF-κ B信号通路的激活因子如S100 A8、PDGF和VEGF抑制TSCC细胞中PI 3 K/Akt/NF-κ B信号通路。此外，miR-22的激活依赖于p53激活时的应激强度。ConclusionsOur findings define miR-22 as a intrinsic molecular switch，通过KAT 6 B/PI 3 K-Akt/ NF-kB途径决定p53依赖的细胞命运。
BackgroundTongue squamous cell carcinoma (TSCC) is the most common oral cancer. Neoadjuvant systemic treatment before or after surgery for advanced TSCC is considered one of the most crucial factors in reducing mortality. However, the therapeutic benefits of chemotherapy are usually attenuated due to intrinsic and/or acquired drug resistance, and a large proportion of TSCC are resistant to chemotherapy, which may result in more aggressive tumor behavior and an even worse clinical outcome. Recently, the potential application of using miRNAs to predict therapeutic response to cancer treatment holds high promise, but miRNAs with predictive value remain to be identified and underlying mechanisms remain to be understood in TSCC.MethodsThe expression of miR-22 in tissues from patients diagnosed with TSCC was analyzed using real-time PCR. The effects of miR-22 on cell proliferation and tumorigenesis in TSCC cells were analyzed by MTS assay, and flow cytometry. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, real-time PCR and western blot were performed to validate a potential target of miR-22 in TC. The correlation between miR-22 expression and KAT6B expression, as well as the mechanisms by which miR-22 regulates PI3k-Akt-NF-kB pathway in TSCC were also addressed.ResultsWe found a strong correlation between miR-22 expression and chemosensitivity to cisplatin (CDDP) in TSCC patients. Ectopic overexpression of miR-22 enhanced TSCC cells apoptosis in response to CDDP in experimental models performed in vitro and in vivo. Moreover, we found that KAT6B is a direct functional target of miR-22. Ectopic expression of KAT6B attenuated the efficiency of miR-22 in TSCC cells upon CDDP treatment. Mechanistically, miR-22 overexpression or KAT6B knockdown inhibited PI3K/Akt/NF-κB signaling in TSCC cells, possibly via downregulating the activators of PI3K/Akt/NF-κB signaling, such as S100A8, PDGF and VEGF. Furthermore, the activation of miR-22 depended on the intensity of the stresses in the presence of p53 activation.ConclusionsOur findings define miR-22 as an intrinsic molecular switch that determines p53-dependent cellular fate through KAT6B/ PI3K-Akt/ NF-kB pathway.
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影响因子：
8
作者：
Patel, J. B.;Appaiah, H. N.;Nakshatri, H.
通讯作者：
Nakshatri, H.
影响因子：
8
作者：
Pelletier, N;Champagne, N;Yang, XJ
通讯作者：
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miR-493的表观遗传沉默通过靶向舌癌耐药相关蛋白1（TCRP1）增加肺癌对顺铂的耐药性
DOI：
10.1186/s13046-017-0582-5
发表时间：
2017-08-31
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Gu Y;Zhang Z;Yin J;Ye J;Song Y;Liu H;Xiong Y;Lu M;Zheng G;He Z
通讯作者：
He Z
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido
miR-639 通过靶向 FOXC1 来调节人舌癌细胞中转化生长因子 β 诱导的上皮间质转化。
影响因子：
5.7
作者：
Lin Z;Sun L;Chen W;Liu B;Wang Y;Fan S;Li Y;Li J
通讯作者：
Li J