[目的]探讨SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的潜在机制。[方法]在TCGA和GEO数据集(GSE12276、GSE2034、GSE2603、GSE5327、GSE14020)中，分析SRSF2在正常组织和HER2阳性乳腺癌组织中的表达水平以及对无远处转移生存的影响。过表达或敲低SRSF2或GLI1后，检测HER2阳性乳腺癌细胞SKBR-3、HCC1419、AU-565的侵袭细胞数。敲低SRSF2后分析GLI1的剪接形式，并且过表达GLI1不同剪接形式(fGLI1和tGLI1)后检测HER2阳性乳腺癌细胞的侵袭细胞数。[结果]在TCGA和GEO数据集中，与正常组织相比，HER2阳性乳腺癌组织中SRSF2的mRNA表达上升5倍(1。00±0。05 vs 5。74±0。37，P＜0。05)。同时，SRSF2高表达的HER2阳性乳腺癌患者具有更短的无远处转移生存(P＜0。05)。过表达SRSF2后，HER2阳性乳腺癌细胞的侵袭细胞数上升2倍(152。88±25。15个vs376。47±32。31个，P＜0。05)。敲低SRSF2后，HER2阳性乳腺癌细胞中fGLI1的mRNA表达上升，tGLI1的mRNA表达下降。过表达tGLI1后，HER2阳性乳腺癌细胞的侵袭细胞数上升3倍(147。43±21。99个vs 397。42±34。03个，P＜0。05)。[结论]SRSF2通过选择性剪接将GLI1剪接成tGL11的形式后，可促进HER2阳性乳腺癌的侵袭能力(152。88±25。15 vs 376。47±32。31，P＜0。05)。
Mechanism of SRSF2/tGLI1 axis regulating invasion of HER2-positive breast cancer
[Objective]To explore the potential mechanism of SRSF2/tGLI1 axis in regulating the invasion of HER2-positive breast cancer.[Method]In TCGA and GEO datasets(GSE12276,GSE2034,GSE2603,GSE5327,GSE14020),the expression levels of SRSF2 in normal tissues and HER2-positive breast cancer tissues were analyzed and the effect on survival without distant metastasis was analyzed.After overexpression or knockdown of SRSF2 or GLI1,the invasion levels of HER2-positive breast cancer cells SKBR-3,HCC1419 and AU-565 were detected.The splicing form of GLI1 was analyzed after knockdown of SRSF2,and the invasion level of HER2-positive breast cancer cells was detected after overexpression of different splicing forms of GLI1(fGLI1 and tGLI1).[Result]In TCGA and GEO datasets,SRSF2 expression was increased in HER2-positive breast cancer tissues compared with normal tissues(1.00±0.05 vs 5.74±0.37,P＜0.05).At the same time,HER2-posi-tive breast cancer patients with high SRSF2 expression had shorter survival without distant metastases(P＜0.05).After SRSF2 overexpression,the invasion level of HER2-positive breast cancer cells increased(152.88±25.15 vs 376.47±32.31,P＜0.05).After SRSF2 knockdown,the expression level of fGLI1 in HER2-positive breast cancer cells increased,and the expres-sion level of tGLI1 decreased.After overexpression of tGLI1,the invasion level of HER2-positive breast cancer cells increased(147.43±21.99 vs 397.42±34.03,P＜0.05).[Conclusion]SRSF2,after splicing GLI1 into tGLI1 via alternative splicing,promoted the invasion of HER2-positive breast cancer(152.88±25.15 vs 376.47±32.31,P＜0.05).
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维普
