<scp>LncRNA‐EWSAT1</scp>promotes hepatocellular carcinoma metastasis via activation of the<scp>Src‐YAP</scp>signaling axis

Chen, Jinggui; Zhou, Jiamin; Mao, Anrong; Xu, Weiqi; Zhu, Hongxu; Pan, Qi; Zhao, Yiming; Zhang, Ning; Wang, Longrong; Wang, Miao; Liu, Zeyang; Zhu, Weiping; Wang, Lu

doi:10.1096/fj.202200825r

Cited by 10 publications

(5 citation statements)

References 28 publications

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“…Knockdown of EWSAT1, an important lncRNA, dramatically suppressed colony formation in soft anger in Ewing sarcoma (A673, SKNMC and TC71) cells(28). The functions of EWSAT1 were subsequently con rmed in other malignant tumors, such as ovarian cancer, hepatocellular carcinoma, colorectal cancer, and cervical cancer (32,33,45,46). In hepatocellular carcinoma, EWSAT1 was signi cantly upregulated compared with that in normal tissue and correlated with an aggressive phenotype and low overall survival.…”

Section: Discussionmentioning

confidence: 97%

LncRNA Inhibits the Viability of Triple-Negative Breast Cancer (TNBC) by Targeting the miR-330-5p/BCL2L2 Axis

Ye,

Fan,

Yang

et al. 2024

Preprint

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Long non-coding RNAs (lncRNAs) play important regulatory roles in the progression of kinds of cancers. However, the biological roles of most lncRNAs in breast cancer, especially TNBC, remain unclear. In this study, we investigated the functional of a novel lncRNA, named lncRNA EWSAT1, in the breast cancer and the underlying molecular mechanisms. EWSAT1 was significantly upregulated in the triple negative breast cancer (TNBC) tissues compared with adjacent normal tissues in the GEO databases. We verified the upregulated level of EWSAT1 in the TNBC patients’ serums compared with healthy serums, which also associated with clinical diagnosis. Bioinformatics analysis demonstrated that microRNA (miR)-330-5p was a potential target of SEAS1. Dual luciferase reporter assays confirmed that EWSAT1 functioned as a sponge for miR-330-5p, regulating the expression of BCL2L2. Moreover, RT-qPCR demonstrated that EWSAT1 negatively regulated the expression of miR-330-5p, and positively regulated the expression of BCL2L2 at transcription and protein level. CCK-8 demonstrated that EWSAT1 could inhibit the viability of TNBC cells. In conclusion, our studies find a functional lncRNA EWSAT1 in the TNBC, and reveal a novel pathway for TNBC treatment via EWSAT1/miR-330-5p/BCL2L2, and suggest EWSAT1 might be a potential biomarkers for TNBC diagnosis and therapeutic target for TNBC.

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Section: Discussionmentioning

confidence: 97%

LncRNA Inhibits the Viability of Triple-Negative Breast Cancer (TNBC) by Targeting the miR-330-5p/BCL2L2 Axis

Ye,

Fan,

Yang

et al. 2024

Preprint

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“…EWSAT1 has been reported to play a pro-tumor role in a variety of cancers. EWSAT1 can contribute to the proliferation and invasion of glioma ( 63 ), promote HCC metastasis ( 64 ), and promote the progression of ovarian cancer ( 65 ). Studies on EWSAT1 in CRC have also been reported.…”

Section: Discussionmentioning

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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“…[79] When the Hippo/YAP signaling pathway is activated, Yes-associated protein (YAP) promotes YAP phosphorylation induced by the sarcoma gene (Src) and further promotes nuclear translocation of YAP, so as to complete transcription against Hippo-YAP signaling target genes involved in cancer evolution. [80] In addition, triplet osteoprotegerin (OPG), receptor activator (RANK) and ligand RANKL that promotes tumor proliferation are also closely related to the occurrence and development of OS. RANKL secreted by tumor cells can bind to receptor RANK on the surface of osteoclasts and promote osteoclasts to differentiate into mature type.…”

Section: Nf-κb Signaling Pathwaymentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of “multiple targets and multiple pathways,” and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/β-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-β (TGF-β)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

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LncRNA‐EWSAT1promotes hepatocellular carcinoma metastasis via activation of theSrc‐YAPsignaling axis

Cited by 10 publications

References 28 publications

LncRNA Inhibits the Viability of Triple-Negative Breast Cancer (TNBC) by Targeting the miR-330-5p/BCL2L2 Axis

LncRNA Inhibits the Viability of Triple-Negative Breast Cancer (TNBC) by Targeting the miR-330-5p/BCL2L2 Axis

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

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

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