Effects of the RNA-binding protein, KSRP, on innate immune response against Helicobacter pylori infection in mice

Li, Ningzhe; Cao, Mei; Yi, Sijun; Cheng, Juan; Wang, Lei; Tao, Yuwei; Wu, Daoyan; Peng, Jingshan; Zhang, Mao; Qi, Panpan; Zhao, Jian

doi:10.1016/j.bbrc.2017.12.016

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…62 This could have potential consequences for the control of antitumor innate immune responses, as similar mechanisms are involved in the recognition of damage-associated molecular patterns and the immunogenicity of tumor cells. 63 Consistently, KHSRP has been implicated in the innate immune response to oncogenic pathogens, such as Helicobacter pylori in the stomach 64 and human papillomavirus in the uterus. 65 One question that remains open is how overexpression of KHSRP is controlled, given that these data suggest it is not the product of a driver mutation event.…”

Section: Discussionmentioning

confidence: 96%

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

Caiazza

Oficjalska

Tosetto

et al. 2019

The American Journal of Pathology

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KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein implicated in key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Using a combination of in silico analysis of large data sets, ex vivo analysis of protein expression in patients, and mechanistic studies using in vitro models of CRC, we investigated the oncogenic role of KHSRP. We demonstrated KHSRP expression in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated expression was found in tumor versus matched normal tissue, and these findings were validated in larger independent cohorts in silico. KHSRP expression was a prognostic indicator of worse overall survival (hazard ratio, 3.74; 95% CI, 1.43e22.97; P Z 0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G 1 /S transition. In addition, KHSRP promoted a proangiogenic extracellular environment by regulating the secretion of oncogenic proteins involved in diverse cellular processes, such as migration and response to cellular stress. Our study provides novel mechanistic insight into the tumor-promoting effects of KHSRP in CRC.

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Section: Discussionmentioning

confidence: 96%

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

Caiazza

Oficjalska

Tosetto

et al. 2019

The American Journal of Pathology

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KH-type splicing regulatory protein controls colorectal cancer cell growth and modulates the tumor microenvironment

Caiazza

Oficjalska

Tosetto

et al. 2018

Preprint

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KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein implicated in key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Using a combination of in silico analysis of large datasets, ex vivo analysis of protein expression in patients, and mechanistic studies using in vitro models of CRC, we investigated the oncogenic role of KHSRP. We demonstrated KHSRP expression in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated expression was found in tumor versus matched normal tissue, and we validated these findings in larger independent cohorts in silico. KHSRP expression was a prognostic indicator of worse overall survival (HR=3.74, 95% CI = 1.43-22.97, p=0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G1/S transition. Additionally, KHSRP promoted a pro-angiogenic extracellular environment by regulating the secretion of oncogenic proteins involved in diverse cellular processes such as migration and response to cellular stress. Our study provides novel mechanistic insight into the tumor-promoting effects of KHSRP in CRC.

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The Role of KH-Type Splicing Regulatory Protein (KSRP) for Immune Functions and Tumorigenesis

Palzer

Bolduan

Käfer

et al. 2022

Cells

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Post-transcriptional control of gene expression is one important mechanism that enables stringent and rapid modulation of cytokine, chemokines or growth factors expression, all relevant for immune or tumor cell function and communication. The RNA-binding protein KH-type splicing regulatory protein (KSRP) controls the mRNA stability of according genes by initiation of mRNA decay and inhibition of translation, and by enhancing the maturation of microRNAs. Therefore, KSRP plays a pivotal role in immune cell function and tumor progression. In this review, we summarize the current knowledge about KSRP with regard to the regulation of immunologically relevant targets, and the functional role of KSRP on immune responses and tumorigenesis. KSRP is involved in the control of myeloid hematopoiesis. Further, KSRP-mediated mRNA decay of pro-inflammatory factors is necessary to keep immune homeostasis. In case of infection, functional impairment of KSRP is important for the induction of robust immune responses. In this regard, KSRP seems to primarily dampen T helper cell 2 immune responses. In cancer, KSRP has often been associated with tumor growth and metastasis. In summary, aside of initiation of mRNA decay, the KSRP-mediated regulation of microRNA maturation seems to be especially important for its diverse biological functions, which warrants further in-depth examination.

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Effects of the RNA-binding protein, KSRP, on innate immune response against Helicobacter pylori infection in mice

Cited by 3 publications

References 28 publications

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

KH-Type Splicing Regulatory Protein Controls Colorectal Cancer Cell Growth and Modulates the Tumor Microenvironment

KH-type splicing regulatory protein controls colorectal cancer cell growth and modulates the tumor microenvironment

The Role of KH-Type Splicing Regulatory Protein (KSRP) for Immune Functions and Tumorigenesis

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