hnRNPC Promotes Malignancy in Pancreatic Cancer through Stabilization of IQGAP3

Abstract

Due to challenges in early-stage detection, aggressive behavior, and poor response to systemic therapy, pancreatic cancer is one of the most fatal cancer types globally. The role of RNA-binding protein (RBP) transcription and translation of cancer cells has been well demonstrated, although their roles in pancreatic cancer is less well understood. In this study, we found that heterogeneous nuclear ribonucleoprotein C (hnRNPC), a RBP, is highly expressed in pancreatic ductal adenocarcinoma (PDAC) tissues and cells. In addition, we discovered that overexpression of hnRNPC in PDAC cells in vitro increased cell proliferation, migration, invasion, and metastasis. The presence of hnRNPC promoted tumorigenesis of pancreatic cells in metastatic in vivo models, which was also validated. In silico analyses revealed that hnRNPC is a strong positive regulator of IQ Motif Containing GTPase Activating Protein 3 (IQGAP3) activity. The experimental confirmation of this association revealed a direct interaction of IQGAP3 and hnRNPC to induce cell growth and invasion in PDAC cells by activating the epithelial-mesenchymal transition. In light of the findings that hnRNPC accelerates PDAC progression by interfering with IQGAP3, it appears that this technique for diagnosis and treatment of PDAC may have promise.

IQ Motif Containing GTPase-Activating Protein 3 Is Associated with Cancer Stemness and Survival in Pancreatic Ductal Adenocarcinoma

“…IQGAP3 expression was not found in the nonneoplastic pancreatic ductal epithelium but in the cytoplasm and cell membranes of cancer cells, suggesting that its expression is relatively specific to cancer. Although elevated expression of IQGAP3 has been previously confirmed in PDAC at the mRNA level [21,32], this report is the first to confirm IQGAP3 protein expression in PDAC using IHC. Moreover, IQGAP3 expression was an independent poor prognostic factor in our immunostaining-based analysis and analyses of the TCGA PAAD dataset.…”

“…It is reported that in the mouse stomach corpus, the IQ-GAP3-ERK-CD44 axis drives stem cell proliferation during homeostasis and tissue repair [38]. A previous study has shown that IQGAP3 acts as an oncogene by regulating Cdc42 expression [21], and heterogeneous nuclear ribonucleoprotein C promotes PDAC progression via IQGAP3 stabilization [32]. It would be desirable to place IQGAP3 in the context of tumor progression by examining the genes associated with IQGAP3, which can be an essential basis for increasing the potential of IQ-GAP3 as a precision therapeutic target.…”

Effect of PTGES3 on the Prognosis and Immune Regulation in Lung Adenocarcinoma

“…In prostate cancer, HNRNPC could promote proliferation and metastasis and inhibit prognosis [ 31 ]. Additionally, upregulation of HNRNPC in metastatic in vivo models could accelerate tumorigenesis in PC [ 32 ]. Moreover, bioinformatics analysis and immunohistochemical staining revealed that HNRNPC was negatively associated with the OS in LUAD [ 33 ].…”

Overexpression of TMEM150A in glioblastoma multiforme patients correlated with dismal prognoses and compromised immune statuses

“…Moreover, TMEM150A expression levels were correlated with immune cell markers such as STAT5A, ITGAM, CCL2, TGFB1, IRF5, FOXP3, CD68, CSF1R, STAT6, HLA-DPB1, GATA3, HLA-DPA1, CD163, STAT3, CD86, IL10, HLA-DRA, CD3-E, ITGAX, MS4A4A, KIR2DL4, HAVCR2, CD2, CD3-D, CTLA4, and others. Additionally, RNA modification genes, such as RBMX, HNRNPC, ALKBH5, and WTAP, play a crucial role in cancer biology [32][33][34][35][36][37][38]. For instance, the inhibition of ALKBH5 expression in GSCs significantly down-regulated stem cell survival and invasion after irradiation and mediated the radioresistant properties of stem cells [33].…”