SRSF2/tGLI1轴调控Her2阳性乳腺癌侵袭的机制

Mechanism of SRSF2/tGLI1 axis regulating invasion of HER2-positive breast cancer

[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vs 376.47±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tGLI1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)。

[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-positive 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 expression 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).