GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC.
GLDC mitigated by miR-30e regulates cell proliferation and tumor immune infiltration in TNBC.
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DOI：
10.3389/fimmu.2022.1033367
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发表时间：
2022
影响因子：
7.3
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Xie, Huaying;Yan, Tingting;Lu, Xinxin;Du, Yueyao;Xu, Shuguang;Kong, Yu;Yu, Liangjie;Sun, Jian;Zhou, Liheng;Ma, Jun
TNBC是一种恶性肿瘤，其临床预后比其他乳腺癌亚组差，其特征在于缺乏雌激素受体、孕激素受体和HER 2过表达。由于缺乏特异性靶向药物，确定参与调节TNBC进展的关键因素至关重要。我们分析了TNBC在TCGA中的表达谱和GLDC的表达值。GLDC和肿瘤免疫浸润的相关性也被确定。CCK 8和BrdU掺入测定用于确定细胞增殖。采用Real-time PCR和Western blot方法检测mRNA和蛋白水平。在本研究中，我们分析了TNBC在TCGA中的mRNA表达谱，发现甘氨酸切割系统的关键酶GLDC在TNBC组织中显著上调，并且GLDC的高表达与TNBC的预后较差相关。TNBC中GLDC的表达与巨噬细胞和单核细胞呈负相关，与活化的CD 4 T细胞和2型辅助性T细胞呈正相关。GLDC的过表达促进TNBC细胞的增殖，而GLDC的敲低具有相反的效果。此外，miR-30 e作为GLDC的功能性上游调节剂，并且miR-30 e对细胞增殖的抑制作用通过GLDC的重新引入而减轻。这些结果表明，miR-30 e抑制的GLDC在TNBC中充当肿瘤抑制途径，并为TNBC的治疗提供了潜在的靶点。
TNBC, whose clinical prognosis is poorer than other subgroups of breast cancer, is a malignant tumor characterized by lack of estrogen receptors, progesterone hormone receptors, and HER2 overexpression. Due to the lack of specific targeted drugs, it is crucial to identify critical factors involved in regulating the progression of TNBC. We analyzed the expression profiles of TNBC in TCGA and the prognoses values of GLDC. Correlations of GLDC and tumor immune infiltration were also identified. CCK8 and BrdU incorporation assays were utilized to determine cell proliferation. The mRNA and protein levels were examined by using Real-time PCR and Western blot analysis. In the present study, we analyzed the mRNA expression profiles of TNBC in TCGA and found that GLDC, a key enzyme in glycine cleavage system, was significantly up-regulated in TNBC tissues and higher expression of GLDC was correlated with a worse prognosis in TNBC. Moreover, the expression of GLDC was negatively correlated with macrophage and monocyte and positively correlated with activated CD4 T cell and type 2 T helper cell in TNBC. Overexpression of GLDC facilitated the proliferation of TNBC cells, whereas GLDC knockdown had the opposite effects. Additionally, miR-30e acts as a functional upstream regulator of GLDC and the inhibitory effects of miR-30e on cell proliferation were mitigated by the reintroduction of GLDC. These results imply that miR-30e-depressed GLDC acts as a tumor suppressive pathway in TNBC and provides potential targets for the treatment of TNBC.
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DOI：
10.2147/bctt.s90627
发表时间：
2015
期刊：
Breast cancer (Dove Medical Press)
影响因子：
--
作者：
Advani P;Cornell L;Chumsri S;Moreno-Aspitia A
通讯作者：
Moreno-Aspitia A
影响因子：
7.3
作者：
Ye Y;Xu C;Chen F;Liu Q;Cheng N
通讯作者：
Cheng N
影响因子：
37.3
作者：
Liu K;Xie F;Gao A;Zhang R;Zhang L;Xiao Z;Hu Q;Huang W;Huang Q;Lin B;Zhu J;Wang H;Que J;Lan X
通讯作者：
Lan X
影响因子：
7.3
作者：
Pachynski, Russell K.;Wang, Ping;Zabel, Brian A.
通讯作者：
Zabel, Brian A.
影响因子：
5.3
作者：
Zhuang L;Shou T;Li K;Gao CL;Duan LC;Fang LZ;Zhang QY;Chen ZN;Zhang C;Yang ST;Li GF
通讯作者：
Li GF