The prognostic value of Cyclin-Dependent Kinase 5 and Protein Phosphatase 2A in Gastric Cancer

Lin, Jiumao; Xie, Xinsheng; Weng, Xing; Zheng, Chao-Hui; Xie, Jian‐Wei; Wang, Jia-Bin; Lu, Jun; Chen, Qi‐Yue; Cao, Long‐Long; Ma, Lin; Tu, Ru‐Hong; Huang, Chang‐Ming; Li, Ping

doi:10.7150/jca.27015

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…We found that TIE1 was upregulated in human cervical cancer and correlated with a poor prognosis. Consistent with our results, it has been indicated that elevated TIE1 expression is associated with a poor prognosis in patients with gastric cancer, ovarian cancer and metastatic breast cancer [30][31][32]. Our functional assays demonstrated that TIE1 promoted cervical cancer growth and metastasis.…”

Section: Discussionsupporting

confidence: 92%

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

Liu,

Xie,

et al. 2024

Int. J. Biol. Sci.

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Background: Tyrosine kinase with immunoglobulin and EGF-like domains 1 (TIE1) is known as an orphan receptor prominently expressed in endothelial cells and participates in angiogenesis by regulating TIE2 activity. Our previous study demonstrated elevated TIE1 expression in cervical cancer cells. However, the role of TIE1 in cervical cancer progression, metastasis and treatment remains elusive. Methods: Immunohistochemistry staining for TIE1 and Basigin was performed in 135 human cervical cancer tissues. Overexpressing vectors and siRNAs were used to manipulate gene expression in tumor cells. Colony formation, wound healing, and transwell assays were used to assess cervical cancer cell proliferation and migration in vitro. Subcutaneous xenograft tumor and lung metastasis mouse models were established to examine tumor growth and metastasis. Co-Immunoprecipitation and Mass Spectrometry were applied to explore the proteins binding to TIE1. Immunoprecipitation and immunofluorescence staining were used to verify the interaction between TIE1 and Basigin. Cycloheximide chase assay and MG132 treatment were conducted to analyze protein stability. Results: High TIE1 expression was associated with poor survival in cervical cancer patients. TIE1 overexpression promoted the proliferation, migration and invasion of cervical cancer cells in vitro, as well as tumor growth and metastasis in vivo. In addition, Basigin, a transmembrane glycoprotein, was identified as a TIE1 binding protein, suggesting a pivotal role in matrix metalloproteinase regulation, angiogenesis, cell adhesion, and immune responses. Knockdown of Basigin or treatment with the Basigin inhibitor AC-73 reversed the tumor-promoting effect of TIE1 in vitro and in vivo. Furthermore, we found that TIE1 was able to interact with and stabilize the Basigin protein and stimulate the Basigin-matrix metalloproteinase axis. Conclusion: TIE1 expression in cervical cells exerts a tumor-promoting effect, which is at least in part dependent on its interaction with Basigin. These findings have revealed a TIE2-independent mechanism of TIE1, which may provide a new biomarker for cervical cancer progression, and a potential therapeutic target for the treatment of cervical cancer patients.

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Section: Discussionsupporting

confidence: 92%

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

Liu,

Xie,

et al. 2024

Int. J. Biol. Sci.

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“…The ER acts as the specific cellular site of synthesis, folding, and structural maturation and trafficking of secretory and cell-surface proteins, and recent evidence showed that impaired ER homeostasis contributed to reproductive physiology and pathology including implantation and placentation, pregnancy complications and preterm birth (Guzel et al 2017). It was reported that CLN8 interacts with protein phosphatase 2A (PP2A) in human fibroblasts (Adhikari et al 2019), and as a major intracellular serine/threonine phosphatase, PP2A regulates a number of signaling pathways, including the cyclins/CDKs pathways (Lin et al 2018, Pippa et al 2020). CCNB1, CCND1 and CCNE1 have been reported to be involved in human EnSCs proliferation (Das 2009), and in the present study, decreased expression levels of these three cyclins were observed in miR-3074-5p-overexpressed T-HESC.…”

Section: Discussionmentioning

confidence: 99%

miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage

et al. 2021

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Decidualization is essential for the successful establishment of pregnancy, and the dysregulated decidualization may lead to early pregnancy loss. It was previously reported by us that miR-3074-5p could promote apoptosis but inhibit invasion of human extravillous trophoblast (EVT) cells in vitro, and the expression level of miR-3074-5p in villus tissues of recurrent miscarriage (RM) patients was significantly increased. The aim of this study was to preliminarily explore the role of miR-3074-5p played in the decidualization of human endometrial stromal cells (ESCs). It was found that the decidual expression level of miR-3074-5p in RM patients was remarkably higher than that in the control group. The overexpression of miR-3074-5p in the immortalized human ESC line, T-HESCs, showed suppressive effects not only on the cell proliferation, as well as the intracellular expression levels of cyclin B1 (CCNB1), CCND1 and CCNE1 but also on the in vitro-induced decidualization. CLN8 mRNA, encoding an endoplasmic reticulum (ER)-associated membrane protein, was validated to be directly targeted by miR-3074-5p. And, the expression level of CLN8 was continuously increased along with the decidualization process, whereas down-regulated CLN8 expression could inhibit the decidualization of T-HESCs in vitro. Furthermore, contrary to the increased expression level of miR-3074-5p, a significantly decreased CLN8 expression was observed in decidual tissues of RM patients. Collectively, these data suggested that an increased miR-3074-5p expression in ESCs might cause early pregnancy failure by disturbing decidualization of ESCs via the miR-3074-5p/CLN8 pathway, providing a potential diagnostic and therapeutic target for RM.

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“…Then, secondary antibody with horseradish peroxidase was added and diaminobenzidine solution was applied, which was followed by 20% hematoxylin. Finally, the IHC signals of these slices were analyzed and scored by two veteran pathologists according to these scoring criteria 57 .…”

Section: Ethics Statement Clinical and Animal Ethics In This Study Wa...mentioning

confidence: 99%

Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin

Wang

et al. 2022

Preprint

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Post-cholecystectomy diarrhea (PCD) is highly prevalent among post-cholecystectomy outpatients and gut microbiota alteration is correlated with it. However, whether fecal bacteria alteration contributes to diarrhea are unrevealed. Herein, humanized gut microbiome mice model was established and PCD mice exhibited enhanced gastrointestinal motility and elevated fecal water content. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. Then, overabundant serotonin, along with elevated biosynthesis and reduced reuptake genes, and highly-expressed 5-HT receptors (5-HTR) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by Tph1 inhibitor and 5-HTRs antagonists. Furthermore, increased PCD microbial secondary bile acids (BAs) metabolites of DCA, HDCA and LCA were revealed and were responsible for stimulating 5-HT. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway alleviate PCD. Conclusively, altered gut microbiota after cholecystectomy induces PCD by promoting secondary BAs, which stimulates colonic 5-HT and increases colon motility.

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The prognostic value of Cyclin-Dependent Kinase 5 and Protein Phosphatase 2A in Gastric Cancer

Cited by 9 publications

References 24 publications

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis

miR-3074-5p/CLN8 pathway regulates decidualization in recurrent miscarriage

Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin

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