NOD1 and NOD2 Are Potential Therapeutic Targets for Cancer Immunotherapy

Abstract

The nucleotide oligomerization domain (NOD)-like receptors (NLRs) are a group of intracellular proteins that are essential for controlling the host's innate immune response. The cytosolic nucleotide binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are the most widely investigated NLRs. As pattern recognition receptors (PRRs), NOD1 and NOD2 may recognize and bind endogenous damage associated molecular patterns (DAMPs) and external pathogenic associated molecular patterns (PAMPs), directing the activation of inflammatory caspases through engaging the adaptor protein RIP2, which further activates the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, thereby mediating host innate immunity and regulating the adaptive immunity. Previous research has identified NOD1 and NOD2 as key players in inflammatory disease and host-microbial defense. Despite numerous studies claiming that NOD1 and NOD2 are linked to tumorigenesis and tumor development, it is still unclear whether NOD1 and NOD2 act as cancer's friends or foes. In this review, we focus on concluding the current research progress on the role of NOD1 and NOD2 in a variety of cancers and discussing the potential reasons for the contradicting role of NOD1 and NOD2 in cancers. This review may help better understand the role of NOD1 and NOD2 in cancer and shed light on NOD1 and NOD2 as potential therapeutic targets for tumor immunotherapy.

Investigation into the Role of Long-Non-Coding RNA MIAT in Leukemia

“…Both HIF-1A and c-MYC were also confirmed to be downregulated upon MIAT silencing in leukemic T cells. The role of HIF-1A in cancer is well reported, and HIF-1A was found to be upregulated in various types of leukemia [ 49 , 50 , 51 , 52 , 53 ]. The upregulation of this gene was also found to activate the NF-κB pathway, and its downregulation led to a decrease in the proliferation and an increase in the inhibition of apoptosis in AML leukemic cell lines [ 49 ].…”

“…The role of HIF-1A in cancer is well reported, and HIF-1A was found to be upregulated in various types of leukemia [ 49 , 50 , 51 , 52 , 53 ]. The upregulation of this gene was also found to activate the NF-κB pathway, and its downregulation led to a decrease in the proliferation and an increase in the inhibition of apoptosis in AML leukemic cell lines [ 49 ]. c-MYC has been extensively associated with oncogenic functions, carcinogenesis, angiogenesis, chemoresistance, and many more cancer-promoting roles [ 54 , 55 ].…”

RIPK2: a promising target for cancer treatment

“…More precisely, NOD1 exerts its anti-tumor effects through the induction of apoptosis, but uncontrolled apoptosis mediated by NOD1 might induce immunosuppression microenvironment, thereby promoting tumor progression. Furthermore, the anti-inflammatory function of NOD2 is dependent on the recognition and binding of bacteria and their derivatives, and when this association is inadequate, NOD2 contributes to chronic inflammation and promotes cancer ( Zhang et al, 2022b ; Wang, 2022 ). Hence, direct targeting NOD1/2 against tumor may result in a therapeutic effect that contradicts expectations.…”

Retracted: NOD1 and NOD2 Are Potential Therapeutic Targets for Cancer Immunotherapy

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”