Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression

Liu, Ying; Li, Yiwen; Du, Chengcheng; Kuang, Shouxiang; Zhou, Xuehao; Zhang, Jinyu; Ao, Xiang

doi:10.1007/s00109-022-02257-5

Cited by 17 publications

(14 citation statements)

References 138 publications

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“…Importantly, cancer cells have evolved multiple strategies to evade immune attack. Cancer cells can reduce antigenicity to disguise as noncancerous cells, hence avoiding the detection by cytotoxic T cells ( 6 , 7 ). They restrict the expression of major histocompatibility complex class I (MHC-I) and costimulatory molecules, rendering cancer cells able to escape from T cell-mediated immunity ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

et al. 2023

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The gastrointestinal tract is inhabited by trillions of commensal microorganisms that constitute the gut microbiota. As a main metabolic organ, the gut microbiota has co-evolved in a symbiotic relationship with its host, contributing to physiological homeostasis. Recent advances have provided mechanistic insights into the dual role of the gut microbiota in cancer pathogenesis. Particularly, compelling evidence indicates that the gut microbiota exerts regulatory effects on the host immune system to fight against cancer development. Some microbiota-derived metabolites have been suggested as potential activators of antitumor immunity. On the contrary, the disequilibrium of intestinal microbial communities, a condition termed dysbiosis, can induce cancer development. The altered gut microbiota reprograms the hostile tumor microenvironment (TME), thus allowing cancer cells to avoid immunosurvelliance. Furthermore, the gut microbiota has been associated with the effects and complications of cancer therapy given its prominent immunoregulatory properties. Therapeutic measures that aim to manipulate the interplay between the gut microbiota and tumor immunity may bring new breakthroughs in cancer treatment. Herein, we provide a comprehensive update on the evidence for the implication of the gut microbiota in immune-oncology and discuss the fundamental mechanisms underlying the influence of intestinal microbial communities on systemic cancer therapy, in order to provide important clues toward improving treatment outcomes in cancer patients.

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Section: Introductionmentioning

confidence: 99%

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

et al. 2023

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“…[31] Also, miRNAs can target 3′UTR of ESRP2 mRNA and regulate its expression in multiple cancer types. [32] Shen et al reported that long noncoding RNAs such as Lnc-LSG1 promotes the ubiquitin-dependent degradation of ESRP2 by binding to ESRP2. [33] In the present study, we found that hypermethylation of the ESRP2 promoter was the major cause of ESRP2 downregulation in HCC, which explains the "turn off" mechanism of oncofetal suppressors in tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Transcription factors such as ZEB1/2 have been shown to regulate ESRP2 expression in non‐small‐cell lung cancer (NSCLC) cells. [31 ] Also, miRNAs can target 3′UTR of ESRP2 mRNA and regulate its expression in multiple cancer types. [32 ] Shen et al.…”

Section: Discussionmentioning

confidence: 99%

Loss of ESRP2 Activates TAK1‐MAPK Signaling through the Fetal RNA‐Splicing Program to Promote Hepatocellular Carcinoma Progression

Yan,

Fang,

Liu

et al. 2023

Advanced Science

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Tumors usually display fetal‐like characteristics, and many oncofetal proteins have been identified. However, fetal‐like reprogramming of RNA splicing in hepatocellular carcinoma (HCC) is poorly understood. Here, it is demonstrated that the expression of epithelial splicing regulatory protein 2 (ESRP2), an RNA splicing factor, is suppressed in fetal hepatocytes and HCC, in parallel with tumor progression. By combining RNA‐Seq with splicing analysis, it is identified that ESRP2 controls the fetal‐to‐adult switch of multiple splice isoforms in HCC. Functionally, ESRP2 suppressed cell proliferation and migration by specifically switching the alternative splicing (AS) of the TAK1 gene and restraining the expression of the fetal and oncogenic isoform, TAK1_ΔE12. Notably, aberrant TAK1 splicing led to the activation of p38MAPK signaling and predicted poor prognosis in HCC patients. Further investigation revealed that TAK1_ΔE12 protein interacted closely with TAB3 and formed liquid condensation in HCC cells, resulting in p38MAPK activation, enhanced cell migration, and accelerated tumorigenesis. Loss of ESRP2 sensitized HCC cells to TAK1 kinase inhibitor (TAK1i), promoting pyroptotic cell death and CD8+ T cell infiltration. Combining TAK1i with immune checkpoint therapy achieved potent tumor regression in mice. Overall, the findings reveal a previously unexplored onco‐fetal reprogramming of RNA splicing and provide novel therapeutic avenues for HCC.

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“…The gut microbiota can trigger inflammatory responses and affect disease outcomes by activating the NLRP3 inflammasome. Changes in the gut microbiota can affect neuroinflammation by activating the NLRP3 inflammasome and promoting the secretion of inflammatory cytokines [57,58]. The interplay between the gut microbiota and the NLRP3 inflammasome in neuroinflammation can be explained by the biological pathways influenced by the gut microbiota-inflammatory response-brain axis.…”

Section: Effects Of the Gut Microbiota On Nlrp3 Inflammatory Responsesmentioning

confidence: 99%

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

Zhang

Flynn

et al. 2022

Nutrients

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The pathophysiological process of intracerebral hemorrhage (ICH) is very complex, involving various mechanisms such as apoptosis, oxidative stress and inflammation. As one of the key factors, the inflammatory response is responsible for the pathological process of acute brain injury and is associated with the prognosis of patients. Abnormal or dysregulated inflammatory responses after ICH can aggravate cell damage in the injured brain tissue. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex distributed in the cytosol, which can be triggered by multiple signals. The NLRP3 inflammasome is activated after ICH, thus promoting neuroinflammation and aggravating brain edema. In addition, there is evidence that the gut microbiota is crucial in the activation of the NLRP3 inflammasome. The gut microbiota plays a key role in a variety of CNS disorders. Changes in the diversity and species of the gut microbiota affect neuroinflammation through the activation of the NLRP3 inflammasome and the release of inflammatory cytokines. In turn, the gut microbiota composition can be influenced by the activation of the NLRP3 inflammasome. Thereby, the regulation of the microbe–gut–brain axis via the NLRP3 inflammasome may serve as a novel idea for protecting against secondary brain injury (SBI) in ICH patients. Here, we review the recent evidence on the functions of the NLRP3 inflammasome and the gut microbiota in ICH, as well as their interactions, during the pathological process of ICH.

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Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression

Cited by 17 publications

References 138 publications

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes

Loss of ESRP2 Activates TAK1‐MAPK Signaling through the Fetal RNA‐Splicing Program to Promote Hepatocellular Carcinoma Progression

Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

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