Caldesmon: Biochemical and Clinical Implications in Cancer

Yao, Yibo; Xiao, Chang-Fang; Lu, Jin-Gen; Wang, Chen

doi:10.3389/fcell.2021.634759

Cited by 11 publications

(12 citation statements)

References 56 publications

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“…Based on these results, MIR100HG regulates the expression of the CALD1 by targeting miR-142-5p. Caldesmon (CALD1) is a cytoskeletal protein that regulates cell morphology and movement through interactions with actin filaments, and is closely related to tumor cell migration, invasion, metastasis and blood vessel formation (Cheng et al, 2021;Yao et al, 2021). Therefore, it has attracted increasing attention of cancer researcher in recent years.…”

Section: Discussionmentioning

confidence: 99%

MIR100HG Regulates CALD1 Gene Expression by Targeting miR-142-5p to Affect the Progression of Bladder Cancer Cells in vitro, as Revealed by Transcriptome Sequencing

Zhang

Wang

et al. 2022

Front. Mol. Biosci.

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Background/Aim: The role of long non-coding RNA (lncRNA) and competing endogenous RNAs (ceRNA) networks in bladder cancer, especially the function of lncRNA-miRNA-mRNA regulatory network in bladder cancer, are still relatively poorly understood. This research mainly used transcriptome sequencing to screen key lncRNAs and ceRNAs, explore their pathogenic mechanism in bladder cancer, and search for potential diagnostic and therapeutic targets.Methods: High-throughput transcriptome sequencing, combined with the limma package, Kaplan-Meier curve analysis, lncRNA-mRNA coexpression network, univariate Cox analysis, multivariate Cox analysis, protein-protein interaction (PPI), functional enrichment, weighed gene co-expression network analysis (WGCNA), ceRNA network and quantitative PCR (qPCR) analyses were performed to assess and screen differentially expressed lncRNAs and mRNAs. Then, the effects of MIR100HG on the proliferation, migration and invasion of the bladder cancer cell line 5,637 were evaluated using cell counting kit-8(CCK-8), wound-healing and transwell assays, respectively. A dual luciferase reporter assay was used to validate the MIR100HG/miR-142-5p and miR-142-5p/CALD1 targeting relationship, and the regulatory relationship among MIR100HG/miR-142-5p/CALD1 expression was explored using qPCR and western blot. Results: A total of 127 differentially expressed lncRNAs and 620 differentially expressed mRNAs were screened. Based on the survival prognosis analysis, Cox analysis, lncRNA-mRNA network, PPI network and WGCNA, we obtained 3 key lncRNAs and 13 key mRNAs, as well as the MIR100HG/miR-142-5p/CALD1 key regulatory axis. qPCR results showed that compared with the adjacent tissues, the expression of MIR100HG and CALD1 was up-regulated, and the expression of miR-142-5p was down-regulated. Moreover, MIR100HG expression was positively correlated with the tumor grade and clinical grade of patients with bladder cancer. Overexpression of MIR100HG effectively promoted the proliferation, migration and invasion of 5,637 cells, inhibited the expression of miR-142-5p, and induced the expression of CALD1 in 5,637 cells. In addition, miR-142-5p inhibited CALD1 expression in bladder cancer cells through a direct association, and reversed the proliferation and CALD1 expression in 5,637 cells overexpressing of MIR100HG.Conclusion: MIR100HG regulates CALD1 expression by targeting miR-142-5p to inhibit the proliferation, migration and invasion of bladder cancer cells. MIR100HG is an independent prognostic factor for bladder cancer, with potential as a biomarker for the diagnosis and treatment of bladder cancer.

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Section: Discussionmentioning

confidence: 99%

MIR100HG Regulates CALD1 Gene Expression by Targeting miR-142-5p to Affect the Progression of Bladder Cancer Cells in vitro, as Revealed by Transcriptome Sequencing

Zhang

Wang

et al. 2022

Front. Mol. Biosci.

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“…Caldesmon has recently attracted attention in cancer due to its roles in cell movement, such as migration, invasion and proliferation [ 20 , 21 ]. l- CALD1 presents in many cell types, except muscle and performance, an essential role in regulating actin dynamics.…”

Section: Discussionmentioning

confidence: 99%

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

Cheng

Tang

Wang

et al. 2021

Cancers

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Angiogenesis is more prominent in anaplastic gliomas and glioblastoma (GBM) than that in pilocytic and diffuse gliomas. Caldesmon (CALD1) plays roles in cell adhesion, cytoskeletal organization, and vascularization. However, limited information is available on mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis. A positive correlation between CALD1 expression and the gliomas’ pathological grade was noticed, according to the samples from the TCGA and CGGA database. Moreover, higher CALD1 expression samples showed worse clinical outcomes than lower CALD1 expression samples. Biofunction prediction suggested that CALD1 may affect glioma progression through modulating tumor angiogenesis. The map of the tumor microenvironment also depicted that more stromal cells, such as endothelial cells and pericytes, infiltrated in high CALD1 expression samples. CALD1 was found to be remarkably upregulated in neoplastic cells and was involved in tumorigenic processes of gliomas in single cell sequencing analysis. Histology and immunofluorescence analysis also indicated that CALD1 associates with vessel architecture, resulting in glioma grade progression. In conclusion, the present study implies that CALD1 may serve as putative marker monitoring the progress of glioma.

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“…To uncover the mechanisms by which Caldesmon localizes to stress fibers, we generated truncated versions of Caldesmon, and expressed those as N-terminal mCherry-fusions in U2OS cells. The N-terminal domain of Caldesmon (residues 1-200), which binds myosin II in vitro 13 and associates with the necks of myosin II bundles in cells (Fig. 2c-f) displayed diffuse cytoplasmic localization with only very weak enrichment to stress fibers.…”

Section: Caldesmon Is An Extended Molecule That Cross-links the Necks...mentioning

confidence: 99%

“…These include actin/myosin-binding protein Caldesmon, which has smooth muscle (H-Caldesmon) and non-muscle cell (L-Caldesmon) specific splice variants. Apart from the ~250 residue regions in the center of H-Caldesmon, the two splice variants are identical to each other 12,13 . The N-terminal ~200 residue region of Caldesmon interacts with both myosin II and calmodulin 14 , and the C-terminal ~200 residue region binds actin filaments, tropomyosin, and calmodulin [15][16][17][18] .…”

mentioning

confidence: 99%

“…Based on biochemical studies, several different functions for Caldesmon were proposed. According to the popular view, Caldesmon regulates actomyosin contractility in a Ca 2+ /calmodulin and phosphorylation-dependent manner and is hence functionally equivalent to the skeletal muscle troponin complex 13 . Caldesmon was additionally proposed to stabilize actin filaments to maintain the structural integrity of actomyosin bundles 22,23 , and stabilize the latchstate of myosin II capable of maintaining force for long periods with low energy consumption 24 .…”

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confidence: 99%

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Caldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments

et al. 2022

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Contractile actomyosin bundles are key force-producing and mechanosensing elements in muscle and non-muscle tissues. Whereas the organization of muscle myofibrils and mechanism regulating their contractility are relatively well-established, the principles by which myosin-II activity and force-balance are regulated in non-muscle cells have remained elusive. We show that Caldesmon, an important component of smooth muscle and non-muscle cell actomyosin bundles, is an elongated protein that functions as a dynamic cross-linker between myosin-II and tropomyosin-actin filaments. Depletion of Caldesmon results in aberrant lateral movement of myosin-II filaments along actin bundles, leading to irregular myosin distribution within stress fibers. This manifests as defects in stress fiber network organization and contractility, and accompanied problems in cell morphogenesis, migration, invasion, and mechanosensing. These results identify Caldesmon as critical factor that ensures regular myosin-II spacing within non-muscle cell actomyosin bundles, and reveal how stress fiber networks are controlled through dynamic cross-linking of tropomyosin-actin and myosin filaments.

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Caldesmon: Biochemical and Clinical Implications in Cancer

Cited by 11 publications

References 56 publications

MIR100HG Regulates CALD1 Gene Expression by Targeting miR-142-5p to Affect the Progression of Bladder Cancer Cells in vitro, as Revealed by Transcriptome Sequencing

MIR100HG Regulates CALD1 Gene Expression by Targeting miR-142-5p to Affect the Progression of Bladder Cancer Cells in vitro, as Revealed by Transcriptome Sequencing

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

Caldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments

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