SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer.
SRPK1/AKT axis promotes oxaliplatin-induced anti-apoptosis via NF-κB activation in colon cancer.
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SRPK1/AKT 轴通过 NF-κ B 激活促进结肠癌中奥沙利铂诱导的抗凋亡
DOI：
10.1186/s12967-021-02954-8
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发表时间：
2021-06-30
影响因子：
7.4
通讯作者：
Gong LY
中科院分区：
文献类型：
--
作者：
Huang JQ;Li HF;Zhu J;Song JW;Zhang XB;Gong P;Liu QY;Zhou CH;Wang L;Gong LY
结直肠癌是第三大常见的诊断。奥沙利铂用作结肠癌的一线治疗。然而，奥沙利铂耐药性大大降低了其治疗效果。SRPK 1参与前体mRNA剪接和肿瘤发生。SRPK 1如何介导结肠癌的耐药性尚不清楚。分析TCGA和CPTAC全癌样品中SRPK 1的表达，并通过IHC和western blot检测结肠癌细胞系和组织中SRPK 1的表达。MTT法和TUNEL法检测细胞的抗凋亡能力。荧光素酶法和qRT-PCR法检测NF-κB的活化。Western blot检测AKT、IKK、IκB及其磷酸化水平。我们发现SRPK 1表达在TCGA和CPTAC泛癌样品中是第二高的。SRPK 1的mRNA和蛋白水平在结肠癌患者的组织中增加。SRPK 1与148例结肠癌患者的临床分期和TNM分期相关。高SRPK 1水平与不良预后相关（p < 0.001）。SRPK 1过表达增强结肠癌细胞的抗凋亡能力，而SRPK 1沉默在奥沙利铂处理下具有相反的效果。SRPK 1在机制上增强IKK激酶和IκB磷酸化，促进NF-κB核转位，从而产生奥沙利铂耐药。我们的研究结果表明SRPK 1参与结肠癌的进展，并通过激活NF-κB通路增强结肠癌细胞的抗凋亡能力，从而诱导结肠癌细胞的耐药，因此可能成为结肠癌治疗的潜在药物靶点。在线版本包含补充材料，可通过10.1186/s12967-021-02954-8获得。
Colorectal cancer is the third most common diagnosis. Oxaliplatin is used as first-line treatment of colon cancer. However, oxaliplatin resistance greatly reduces its therapeutic effect. SRPK1 involves in pre-mRNA splicing and tumorigenesis. How SRPK1 mediates drug resistance in colon cancer is unknown. The expression of SRPK1 was analyzed in the TCGA and the CPTAC pan-cancer samples and detected in colon cancer cell lines and tissues by IHC and western blot. The MTT and TUNEL assay were used to verify the anti-apoptosis ability of colon cancer cell. The activation of NF-κB was determined by luciferase assay and qRT-PCR. AKT, IKK, IκB and their phosphorylation level were verified by western blot. We found that SRPK1 expression was the second highest in TCGA and the CPTAC pan-cancer samples. The mRNA and protein levels of SRPK1 were increased in tissues from patients with colon cancer. SRPK1 was associated with clinical stage and TNM classifications in 148 cases of colon cancer patients. High SRPK1 levels correlated with poor prognosis (p < 0.001). SRPK1 overexpression enhanced the anti-apoptosis ability of colon cancer cells, whereas SRPK1 silencing had the opposite effect under oxaliplatin treatment. Mechanistically, SRPK1 enhances IKK kinase and IκB phosphorylation to promote NF-κB nuclear translocation to confer oxaliplatin resistance. Our findings suggest that SRPK1 participates in colon cancer progression and enhances the anti-apoptosis capacity to induce drug resistance in colon cancer cells via NF-κB pathway activation, and thus might be a potential pharmaceutically target for colon cancer treatment. The online version contains supplementary material available at 10.1186/s12967-021-02954-8.
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影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
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影响因子：
7.3
作者：
Gong, Liyun;Song, Junwei;Song, Libing
通讯作者：
Song, Libing
影响因子：
3.2
作者：
Krishnakumar, Subramanian;Mohan, Adithi;Das, Radha R.
通讯作者：
Das, Radha R.
影响因子：
2.9
作者：
Gassmann, Max;Grenacher, Beat;Vogel, Johannes
通讯作者：
Vogel, Johannes
影响因子：
14.9
作者：
Labourier, E;Rossi, F;Tazi, J
通讯作者：
Tazi, J