PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma

Wang, Pusen; Jiang, Zhongyi; Liu, Xueni; Yu, Kanru; Wang, Chunguang; Li, Hao; Zhong, Lin

doi:10.1002/cam4.3331

Cited by 10 publications

(10 citation statements)

References 31 publications

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“…Crawford et al found that overexpression of Pi16 significantly inhibited breast cancer tumorigenesis and metastasis 32 . Wang et al found that knocking down Pi16 could significantly inhibit apoptosis and thus increase the sensitivity of hepatocellular carcinoma to sorafenib therapy 10 . In addition, Pi16 works through multiple pathways, such as regulating the activation of p53 signaling pathways or acting as a protease inhibitor of cathepsin K and MMP2 33 .…”

Section: Discussionmentioning

confidence: 99%

“…Studies have found that Pi16 is expressed in a variety of tissues, including cardiomyocytes, the digestive tract, and the testes, and is involved in a variety of pathophysiological processes, including fibrosis, immune regulation, and signal transduction 7–9 . In recent years, studies have shown that Pi16 can regulate the occurrence and metastasis of tumors by targeting the p38/MAPK pathway, the NEMO/NF‐κB axis, or other mechanisms 10,11 . In addition, Pi16, as an independent risk factor for prognostic judgment, has certain value in guiding the clinical treatment of prostate cancer and hepatocellular carcinoma 10,12 .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] In recent years, studies have shown that Pi16 can regulate the occurrence and metastasis of tumors by targeting the p38/MAPK pathway, the NEMO/NF-κB axis, or other mechanisms. 10,11 In addition, Pi16, as an independent risk factor for prognostic judgment, has certain value in guiding the clinical treatment of prostate cancer and hepatocellular carcinoma. 10,12 In summary, understanding the role of Pi16 may provide new clues by which we can explore the mechanisms of tumors.…”

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confidence: 99%

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Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling

Chen,

Jiang,

Cao

et al. 2024

Molecular Carcinogenesis

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Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis and a 5‐year survival rate of less than 11%. As a member of the CAP superfamily of proteins, the role of peptidase inhibitor 16 (Pi16) in tumor progression is still unclear. Immunohistochemistry and quantitative RT‐PCR methods were used to detect the expression levels of Pi16 protein and mRNA in PDAC patients. CRISPR/Cas9 technology was used to knock out the expression of Pi16 in PDAC cell lines. In vivo and in vitro experiments were used to verify the effect of Pi16 on PDAC proliferation ability. By RNA sequencing, we found that oligoadenylate synthetase L (OASL) can serve as a potential downstream target of Pi16. The expression of Pi16 was higher in PDAC tissues than in matched adjacent tissues. High expression of Pi16 was associated with PDAC progression and poor prognosis. Overexpression of Pi16 could promote the proliferation of PDAC cells in vitro and in vivo. Bioinformatics analysis and coimmunoprecipitation assays showed that Pi16 could bind to OASL. Moreover, the functional recovery test confirmed that Pi16 could promote the proliferation of PDAC via OASL. Our present study demonstrates that Pi16 might participate in the occurrence and development of PDAC by regulating cell proliferation by binding to OASL, indicating that Pi16 might be a promising novel therapeutic target for PDAC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling

Chen,

Jiang,

Cao

et al. 2024

Molecular Carcinogenesis

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“…scorpions, Cid-Uribe et al, 2018 ). Whereas its role in venoms is still unknown, in humans PI16 expression has been connected to conditions including heart disease ( Frost & Engelhardt, 2007 ), cancer ( Wang et al, 2020 ), and inflammation ( Hazell et al, 2016 ). PI16 prevents the proteolytic activation of chemerin, a protein involved in recruiting macrophages to sites of inflammation ( Regn et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

The cnidarian parasite Ceratonova shasta utilizes inherited and recruited venom-like compounds during infection

Americus

Hams

Klompen

et al. 2021

PeerJ

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Background Cnidarians are the most ancient venomous organisms. They store a cocktail of venom proteins inside unique stinging organelles called nematocysts. When a cnidarian encounters chemical and physical cues from a potential threat or prey animal, the nematocyst is triggered and fires a harpoon-like tubule to penetrate and inject venom into the prey. Nematocysts are present in all Cnidaria, including the morphologically simple Myxozoa, which are a speciose group of microscopic, spore-forming, obligate parasites of fish and invertebrates. Rather than predation or defense, myxozoans use nematocysts for adhesion to hosts, but the involvement of venom in this process is poorly understood. Recent work shows some myxozoans have a reduced repertoire of venom-like compounds (VLCs) relative to free-living cnidarians, however the function of these proteins is not known. Methods We searched for VLCs in the nematocyst proteome and a time-series infection transcriptome of Ceratonova shasta, a myxozoan parasite of salmonid fish. We used four parallel approaches to detect VLCs: BLAST and HMMER searches to preexisting cnidarian venom datasets, the machine learning tool ToxClassifier, and structural modeling of nematocyst proteomes. Sequences that scored positive by at least three methods were considered VLCs. We then mapped their time-series expressions in the fish host and analyzed their phylogenetic relatedness to sequences from other venomous animals. Results We identified eight VLCs, all of which have closely related sequences in other myxozoan datasets, suggesting a conserved venom profile across Myxozoa, and an overall reduction in venom diversity relative to free-living cnidarians. Expression of the VLCs over the 3-week fish infection varied considerably: three sequences were most expressed at one day post-exposure in the fish’s gills; whereas expression of the other five VLCs peaked at 21 days post-exposure in the intestines, coinciding with the formation of mature parasite spores with nematocysts. Expression of VLC genes early in infection, prior to the development of nematocysts, suggests venoms in C. shasta have been repurposed to facilitate parasite invasion and proliferation within the host. Molecular phylogenetics suggested some VLCs were inherited from a cnidarian ancestor, whereas others were more closely related to sequences from venomous non-Cnidarian organisms and thus may have gained qualities of venom components via convergent evolution. The presence of VLCs and their differential expression during parasite infection enrich the concept of what functions a “venom” can have and represent targets for designing therapeutics against myxozoan infections.

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“…Wang et al recently published their data about the role of PI16, a gene with differential expression in many tumor cells; low levels of PI16 were significantly associated with longer PFS and OS in patients treated with sorafenib, suggesting its possible value as a predictive biomarker [ 105 ].…”

Section: Unmet Needs and Future Perspectivesmentioning

confidence: 99%

The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review

et al. 2021

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Hepatocellular carcinoma (HCC) is the main type of liver cancer. In the majority of cases, HCC is diagnosed at the advanced stage, leading to poor prognosis. In recent years, many efforts have been devoted to investigating potential new and more effective drugs and, indeed, the treatment armamentarium for advanced HCC has broadened tremendously, with targeted- and immune-therapies, and probably the combination of both, playing pivotal roles. Together with new established knowledge, many issues are emerging, with the role of neoadjuvant/adjuvant settings, the definition of the best transitioning time from loco-regional treatments to systemic therapy, the identification of potential predictive biomarkers, and radiomics being just some of the topics that will have to be further explored in the next future. Clearly, the current COVID-19 pandemic has influenced the management of HCC patients and some considerations about this topic will be elucidated.

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PI16 attenuates response to sorafenib and represents a predictive biomarker in hepatocellular carcinoma

Cited by 10 publications

References 31 publications

Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling

Peptidase inhibitor 16 promotes proliferation of pancreatic ductal adenocarcinoma cells through OASL signaling

The cnidarian parasite Ceratonova shasta utilizes inherited and recruited venom-like compounds during infection

The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review

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