Comprehensive Analyses of the Immunological and Prognostic Roles of an IQGAP3AR/let-7c-5p/IQGAP3 Axis in Different Types of Human Cancer

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.

Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer

“…Its similar action has been reported in hepatocellular carcinoma, since sponging let-7c-5p has been associated with tumor proliferation and invasion [78]. In agreement with our results, let-7c-5p overexpression has been correlated with (i) a good prognosis in other gastrointestinal cancers, such as oesophageal carcinoma, as well as (ii) sensitivity to anticancer therapy [79]. Although hsa-let-7d-5p has not been studied so far in colorectal cancer drug response, its overexpression has been linked with sensitivity to tivantinib in breast cancer cell lines [80].…”

Structural variation and eQTL analysis in two experimental populations of chickens divergently selected for feather-pecking behavior

“…With 53 genome-wide associations, an intergenic TR seemed to have an impact on more than half of the top DEGs between HFP and LFP whole brains. The variant is located 2.7 kb downstream of the E3 ubiquitin ligase ENSGALG00000055092 (DCAF11) and 7.5 kb upstream of IQGAP3, which is required for proper cell cycle progression [76] and which influences immune cell infiltration and immune modulators [77]. A 294-bp intron deletion in RO60, a gene involved in the regulation of inflammatory gene expression [78], was associated with 30 DEGs, which might be responsible for the observation that 48.1% of DEGs between HFP and LFP belong to the PANTHER protein class defense/immunity (PC00090) [1].…”

Identification and Validation of Hub Genes in Uterine Corpus Endometrioid Carcinoma

“…Studies have found that the expression of IQGAP3 is increased in highgrade serous ovarian cancer, and the proliferation, migration and invasion of ovarian cancer cell are inhibited when IQGAP3 is silenced [28] . Interestingly, high expression of IQGAP3 appears to be associated with tumor mutational burden, microsatellite instability, immune cell in ltration, and immunomodulatory agents, with integral roles in the progression and immune response of various human cancers [29] . IQGAP3 expression was negatively correlated with Dendritic cells resting, but positively correlated with B cells naive.…”