Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling

Xu, Renjie; Yu, Jiahui; Song, Shangjin; Sun, Dongmei; Xiu, Lijuan; Xu, Jianrong; Zhao, Jing; Li, Xuan; Ji, Qing; Yue, Xiaoqiang

doi:10.7150/ijms.76664

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…PAR‐1 could promote pancreatic cancer cells' migration, invasion ability, and EMT (H. Liu et al., 2020). Inhibiting PAR‐1 can further inhibit proliferation and promote cell death of gastric cancer cells (Xu et al., 2022). Same as these results, our study found knockdown PAR‐1 could promote inflammatory factors and apoptotic of SUDHL2, inhibited proliferation, migration, and invasion of SUDHL2, and its results were the same when DLBCL cells were hypoxic.…”

Section: Discussionmentioning

confidence: 99%

Recombinant hirudin suppresses angiogenesis of diffuse large B‐cell lymphoma through regulation of the PAR‐1‐VEGF

Zhao,

Li,

Zhang

et al. 2024

Chem Biol Drug Des

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Hirudin is one of the specific inhibitors of thrombin, which has been confirmed to have strong bioactivities, including inhibiting tumors. However, the function and mechanism of hirudin and protease‐activated receptor 1 (PAR‐1) in diffuse large B‐cell lymphoma (DLBCL) have not been clear. Detecting the expression PAR‐1 in DLBCL tissues and cells by RT‐qPCR and IHC. Transfected sh‐NC, sh‐PAR‐1, or pcDNA3.1‐PAR‐1 in DLBCL cells or processed DLBCL cells through added thrombin, Vorapaxar, Recombinant hirudin (RH), or Na2S2O4 and co‐culture with EA.hy926. And built DLBCL mice observed tumor growth. Detecting the expression of related genes by RT‐qPCR, Western blot, IHC, and immunofluorescence, measured the cellular hypoxia with Hypoxyprobe‐1 Kit, and estimated the cell inflammatory factors, proliferation, migration, invasion, and apoptosis by ELISA, CCK‐8, flow cytometry, wound‐healing and Transwell. Co‐immunoprecipitation and pull‐down measurement were used to verify the relationship. PAR‐1 was highly expressed in DLBCL tissues and cells, especially in SUDHL2. Na2S2O4 induced SUDHL2 hypoxia, and PAR‐1 did not influence thrombin‐activated hypoxia. PAR‐1 could promote SUDHL2 proliferation, migration, and invasion, and it was unrelated to cellular hypoxia. PAR‐1 promoted proliferation, migration, and angiogenesis of EA.hy926 or SUDHL2 through up‐regulation vascular endothelial growth factor (VEGF). RH inhibited tumor growth, cell proliferation, and migration, promoted apoptosis of DLBCL, and inhibited angiogenesis by down‐regulating PAR‐1‐VEGF. RH inhibits proliferation, migration, and angiogenesis of DLBCL cells by down‐regulating PAR‐1‐VEGF.

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Section: Discussionmentioning

confidence: 99%

Recombinant hirudin suppresses angiogenesis of diffuse large B‐cell lymphoma through regulation of the PAR‐1‐VEGF

Zhao,

Li,

Zhang

et al. 2024

Chem Biol Drug Des

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“…Crucially, non‐coding RNA‐mediated epigenetic modifications play an important role in the process of GC cell apoptosis, including long non‐coding RNA (lncRNA) (Xiao et al, 2022), micro‐RNA (miR) (Kipkeeva et al, 2020), and circular RNA (circRNA) (Li, Yang, & Xu, 2020c). For instance, lncRNA‐ncRuPAR was shown to promote apoptosis in human GC cells by inhibiting PAR‐1, PI3K/Akt signaling and cyclin D1 (Xu, Yu, et al, 2022b). MiR‐874‐3p, sponged by LINC00922, was found to inhibit GC progression by targeting glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) and promoting apoptosis (Zhang, Dai, et al, 2022e).…”

Section: Insights Into Rcds In Gcmentioning

confidence: 99%

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives

et al. 2023

Phytotherapy Research

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Gastric cancer (GC) is one of the most serious gastrointestinal malignancies with high morbidity and mortality. The complexity of GC process lies in the multi‐phenotypic linkage regulation, in which regulatory cell death (RCD) is the core link, which largely dominates the fate of GC cells and becomes a key determinant of GC development and prognosis. In recent years, increasing evidence has been reported that natural products can prevent and inhibit the development of GC by regulating RCDs, showing great therapeutic potential. In order to further clarify its key regulatory characteristics, this review focused on specific expressions of RCDs, combined with a variety of signaling pathways and their crosstalk characteristics, sorted out the key targets and action rules of natural products targeting RCD. It is highlighted that a variety of core biological pathways and core targets are involved in the decision of GC cell fate, including the PI3K/Akt signaling pathway, MAPK‐related signaling pathways, p53 signaling pathway, ER stress, Caspase‐8, gasdermin D (GSDMD), and so on. Moreover, natural products target the crosstalk of different RCDs by modulating above signaling pathways. Taken together, these findings suggest that targeting various RCDs in GC with natural products is a promising strategy, providing a reference for further clarifying the molecular mechanism of natural products treating GC, which warrants further investigations in this area.

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“…F11-AS1 regulates the expression of PTEN through competitive binding with miR-3146 , thereby inhibiting the progression of LIHC ( 22 ). Another CRL, ncRuPAR (non-protein coding RNA, upstream of coagulation factor II thrombin receptor [F2R]/protease-activated receptor-1 [PAR-1]), can inhibit tumor cell proliferation and promote apoptosis of human gastric cancer cells by inhibiting PAR-1, PI3K/Akt signaling, and cyclin D1, and its downregulation can promote angiogenesis, invasion, metastasis, and progression ( 23 , 24 ). However, it is not clear whether CRLs have a regulatory effect on the occurrence and development of CRC.…”

Section: Introductionmentioning

confidence: 99%

Computational identification and clinical validation of a novel risk signature based on coagulation-related lncRNAs for predicting prognosis, immunotherapy response, and chemosensitivity in colorectal cancer patients

Zhang,

Zong

et al. 2023

Front. Immunol.

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BackgroundCoagulation is critically involved in the tumor microenvironment, cancer progression, and prognosis assessment. Nevertheless, the roles of coagulation-related long noncoding RNAs (CRLs) in colorectal cancer (CRC) remain unclear. In this study, an integrated computational framework was constructed to develop a novel coagulation-related lncRNA signature (CRLncSig) to stratify the prognosis of CRC patients, predict response to immunotherapy and chemotherapy in CRC, and explore the potential molecular mechanism.MethodsCRC samples from The Cancer Genome Atlas (TCGA) were used as the training set, while the substantial bulk or single-cell RNA transcriptomics from Gene Expression Omnibus (GEO) datasets and real-time quantitative PCR (RT-qPCR) data from CRC cell lines and paired frozen tissues were used for validation. We performed unsupervised consensus clustering of CRLs to classify patients into distinct molecular subtypes. We then used stepwise regression to establish the CRLncSig risk model, which stratified patients into high- and low-risk groups. Subsequently, diversified bioinformatics algorithms were used to explore prognosis, biological pathway alteration, immune microenvironment, immunotherapy response, and drug sensitivity across patient subgroups. In addition, weighted gene coexpression network analysis was used to construct an lncRNA–miRNA–mRNA competitive endogenous network. Expression levels of CRLncSig, immune checkpoints, and immunosuppressors were determined using RT-qPCR.ResultsWe identified two coagulation subclusters and constructed a risk score model using CRLncSig in CRC, where the patients in cluster 2 and the low-risk group had a better prognosis. The cluster and CRLncSig were confirmed as the independent risk factors, and a CRLncSig-based nomogram exhibited a robust prognostic performance. Notably, the cluster and CRLncSig were identified as the indicators of immune cell infiltration, immunoreactivity phenotype, and immunotherapy efficiency. In addition, we identified a new endogenous network of competing CRLs with microRNA/mRNA, which will provide a foundation for future mechanistic studies of CRLs in the malignant progression of CRC. Moreover, CRLncSig strongly correlated with drug susceptibility.ConclusionWe developed a reliable CRLncSig to predict the prognosis, immune landscape, immunotherapy response, and drug sensitivity in patients with CRC, which might facilitate optimizing risk stratification, guiding the applications of immunotherapy, and individualized treatments for CRC.

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Long non-coding RNA ncRuPAR regulates gastric cancer cell proliferation and apoptosis via phosphoinositide 3-kinase/protein kinase B signaling

Cited by 5 publications

References 31 publications

Recombinant hirudin suppresses angiogenesis of diffuse large B‐cell lymphoma through regulation of the PAR‐1‐VEGF

Recombinant hirudin suppresses angiogenesis of diffuse large B‐cell lymphoma through regulation of the PAR‐1‐VEGF

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives

Computational identification and clinical validation of a novel risk signature based on coagulation-related lncRNAs for predicting prognosis, immunotherapy response, and chemosensitivity in colorectal cancer patients

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