关键词: IQGAP3 human cancer immunotherapy let-7c-5p prognosis

来  源:   DOI:10.3389/fmolb.2022.763248   PDF(Pubmed)

Abstract:
IQ motif containing GTPase-activating protein 3 (IQGAP3) is a member of the Rho family of guanosine-5\'-triphosphatases (GTPases). IQGAP3 plays a crucial part in the development and progression of several types of cancer. However, the prognostic, upstream-regulatory, and immunological roles of IQGAP3 in human cancer types are not known. We found that IQGAP3 expression was increased in different types of human cancer. The high expression of IQGAP3 was correlated with tumor stage, lymph node metastasis, and a poor prognosis in diverse types of human cancer. The DNA methylation of IQGAP3 was highly and negatively correlated with IQGAP3 expression in diverse cancer types. High DNA methylation in IQGAP3 was correlated with better overall survival in human cancer types. High mRNA expression of IQGAP3 was associated with tumor mutational burden, microsatellite instability, immune cell infiltration, and immune modulators. Analyses of signaling pathway enrichment showed that IQGAP3 was involved in the cell cycle. IQGAP3 expression was associated with sensitivity to a wide array of drugs in cancer cells lines. We revealed that polypyrimidine tract-binding protein 1 (PTBP1) and an IQGAP3-associated lncRNA (IQGAP3AR)/let-7c-5p axis were potential regulations for IQGAP3 expression. We provided the first evidence to show that an IQGAP3AR/let-7c-5p/IQGAP3 axis has indispensable roles in the progression and immune response in different types of human cancer.
摘要:
含有GTPase激活蛋白3(IQGAP3)的IQ基序是鸟苷-5'-三磷酸酶(GTPases)Rho家族的成员。IQGAP3在几种癌症的发展和进展中起着至关重要的作用。然而,预后,上游监管,IQGAP3在人类癌症类型中的免疫学作用尚不清楚。我们发现IQGAP3表达在不同类型的人类癌症中增加。IQGAP3的高表达与肿瘤分期有关。淋巴结转移,在不同类型的人类癌症中预后不良。在不同类型的癌症中,IQGAP3的DNA甲基化与IQGAP3表达高度负相关。IQGAP3中的高DNA甲基化与人类癌症类型中更好的总体生存率相关。IQGAP3mRNA的高表达与肿瘤突变负荷有关,微卫星不稳定,免疫细胞浸润,和免疫调节剂。信号通路富集分析表明IQGAP3参与细胞周期。IQGAP3表达与癌细胞系中对多种药物的敏感性相关。我们发现多嘧啶束结合蛋白1(PTBP1)和IQGAP3相关的lncRNA(IQGAP3AR)/let-7c-5p轴是IQGAP3表达的潜在调控。我们提供了第一个证据表明IQGAP3AR/let-7c-5p/IQGAP3轴在不同类型的人类癌症的进展和免疫应答中具有不可或缺的作用。
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