LncCCLM inhibits lymphatic metastasis of cervical cancer by promoting STAU1-mediated IGF-1 mRNA degradation

Chen, Chen; Shen, Ningmei; Chen, Yali; Jiang, Pinping; Sun, Wei; Wang, Qiang; Wang, Zhangding; Jiang, Yi; Cheng, Wenjun; Fu, Shilong; Wang, Shouyu

doi:10.1016/j.canlet.2021.07.005

Cited by 19 publications

(15 citation statements)

References 28 publications

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“…Nuclear factor (NF-κb) -VEGF-C pathway participates in the lymphangiogenesis of gallbladder carcinoma, and VEGF-C is activated in response to proinflammatory cytokines such as TNFα (Li et al, 2018). IGF-1 is related to lymphangiogenesis, and Chen found that LncCCLM could reduce lymphangiogenesis and lymphatic metastasis in cervical cancer by accelerating the degradation of IGF-1 mRNA (Chen et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis

Peng

Ma²,

Dong³

et al. 2022

Front. Pharmacol.

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Background: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), which is associated with lymphangiogenesis deficiency. In this study, we comprehensively verified whether KXF promotes lymphangiogenesis in zebrafish and in vitro based on network analysis.Methods: We performed virtual screening of the active compounds of KXF and potential targets regarding DCM based on network analysis. Tg (Flila: EGFP; Gata1: DsRed) transgenic zebrafish embryos were treated with different concentrations of KXF for 48 h with or without the pretreatment of MAZ51 for 6 h, followed by morphological observation of the lymphatic vessels and an assessment of lymphopoiesis. RT-qPCR was employed to identify VEGF-C, VEGF-A, PROX1, and LYVE-1 mRNA expression levels in different groups. After the treatment of lymphatic endothelial cells (LECs) with different concentrations of salvianolic acid B (SAB, the active ingredient of KXF), their proliferation, migration, and protein expression of VEGF-C and VEGFR-3 were compared by CCK-8 assay, wound healing assay, and western blot.Results: A total of 106 active compounds were identified constituting KXF, and 58 target genes of KXF for DCM were identified. There were 132 pathways generated from KEGG enrichment, including 5 signaling pathways related to lymphangiogenesis. Zebrafish experiments confirmed that KXF promoted lymphangiogenesis and increased VEGF-C and VEGF-A mRNA expression levels in zebrafish with or without MAZ51-induced thoracic duct injury. In LECs, SAB promoted proliferation and migration, and it could upregulate the protein expression of VEGF-C and VEGFR-3 in LECs after injury.Conclusion: The results of network analysis showed that KXF could regulate lymphangiogenesis through VEGF-C and VEGF-A, and experiments with zebrafish confirmed that KXF could promote lymphangiogenesis. Cell experiments confirmed that SAB could promote the proliferation and migration of LECs and upregulate the protein expression of VEGF-C and VEGFR-3. These results suggest that KXF promotes lymphangiogenesis by a mechanism related to the upregulation of VEGF-C/VEGFR-3, and the main component exerting this effect may be SAB.

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Section: Discussionmentioning

confidence: 99%

Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis

Peng

Ma²,

Dong³

et al. 2022

Front. Pharmacol.

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“…LncRNA NR2F1-AS1 can also lead to IGF1R activation by sponging miR-338-3p, which downegulates IGF-1 [27]. LncRNA CCLM interacts with the RNA-binding protein STAU-1, promoting its degradation of IGF-1 mRNA [28]. H19 suppression by promoter methylation leads to an increase in IGF-2 expression [31].…”

Section: H19mentioning

confidence: 99%

Noncoding RNA actions through IGFs and IGF binding proteins in cancer

Kerr

Baxter

2022

Oncogene

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The insulin-like growth factors (IGFs) and their regulatory proteins—IGF receptors and binding proteins—are strongly implicated in cancer progression and modulate cell survival and proliferation, migration, angiogenesis and metastasis. By regulating the bioavailability of the type-1 IGF receptor (IGF1R) ligands, IGF-1 and IGF-2, the IGF binding proteins (IGFBP-1 to -6) play essential roles in cancer progression. IGFBPs also influence cell communications through pathways that are independent of IGF1R activation. Noncoding RNAs (ncRNAs), which encompass a variety of RNA types including microRNAs (miRNAs) and long-noncoding RNAs (lncRNAs), have roles in multiple oncogenic pathways, but their many points of intersection with IGF axis functions remain to be fully explored. This review examines the functional interactions of miRNAs and lncRNAs with IGFs and their binding proteins in cancer, and reveals how the IGF axis may mediate ncRNA actions that promote or suppress cancer. A better understanding of the links between ncRNA and IGF pathways may suggest new avenues for prognosis and therapeutic intervention in cancer. Further, by exploring examples of intersecting ncRNA-IGF pathways in non-cancer conditions, it is proposed that new opportunities for future discovery in cancer control may be generated.

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“…Long noncoding RNAs (lncRNAs) are epigenetic factors that are implicated in diverse human diseases, including CC. − lncRNAs are defined as a group of mRNA-like nonprotein coding transcripts with lengths longer than 200 nucleotides. , To date, an increasing number of lncRNAs have been discovered through functional genomic studies. Although the function of most lncRNAs remains unclear, increasing evidence has demonstrated that lncRNAs play critical roles in a variety of cellular processes, including cell proliferation, cell cycle, and cell apoptosis. − It was proposed that lncRNAs are involved in regulating cell signaling pathways and gene expression by altering transcription, translation, protein modification, and the formation of RNA–protein or protein–protein complexes. − Moreover, lncRNAs are ubiquitously expressed in all eukaryotic cells and exhibit diverse profiles in different types of cancer, including CC. − Among them, BRAF-activated noncoding RNA (BANCR) stands out as an oncogenic lncRNA and is involved in various cancers. , …”

Section: Introductionmentioning

confidence: 99%

Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells

Wang

Jia

et al. 2022

J. Proteome Res.

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Long noncoding RNAs (lncRNAs) are increasingly recognized as functional regulators of human cancers. BRAF-activated noncoding RNA (BANCR), an oncogenic lncRNA, has a carcinogenic effect on many types of cancers. However, the clinical significance and molecular mechanisms of BANCR in cervical cancer are still unclear. Here, we generated BANCR knockout cell lines via CRISPR/Cas9 editing and revealed that BANCR plays roles in the apoptosis, proliferation, and migration of HeLa cells. A quantitative proteomics strategy was employed to globally identify BANCR-regulated proteins in HeLa cells. In total, we identified 569 differentially expressed proteins (DEPs) upon knockout of BANCR in HeLa cells. Bioinformatic analysis revealed that these DEPs were involved in diverse cellular pathways. Functional studies revealed that BANCR exerts its effects on the proliferation and apoptosis of HeLa cells through the regulation of cAMP-responsive element binding protein 1 (CREB1) expression. Mechanistically, BANCR could inhibit the expression of miR-582-5p, and CREB1 is a direct target of miR-582-5p; therefore, BANCR may exert its function by regulating CREB1 expression via targeting miR-582-5p in cervical cancer cells. Collectively, this study established a proteome-wide BANCR regulatory network, which provides novel insight into the molecular pathogenesis of cervical cancer and can serve as a basis for the development of targeted therapies.

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LncCCLM inhibits lymphatic metastasis of cervical cancer by promoting STAU1-mediated IGF-1 mRNA degradation

Cited by 19 publications

References 28 publications

Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis

Kuoxin Decoction promotes lymphangiogenesis in zebrafish and in vitro based on network analysis

Noncoding RNA actions through IGFs and IGF binding proteins in cancer

Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells

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