Collagen Triple Helix Repeat Containing 1 Research Articles

CTHRC1 Attenuates Tendinopathy via Enhancing EGFR/MAPK Signaling Pathway.

Tendinopathy poses a formidable challenge due to the inherent limitations of tendon regenerative capabilities post-injury. At present, effective curative approaches for tendinopathy are still lacking. Collagen triple helix repeat-containing 1 (CTHRC1) is an extracellular matrix protein with significant roles in both physiological and pathological processes. The present study aims to investigate the function and underlying mechanism of CTHRC1 in tendinopathy. In this study, CTHRC1 is identified as a potential effector in promoting tendon regeneration through multi-proteomic analysis of Achilles tendon tissues in mice. In vitro, CTHRC1 enhances the proliferation, migration, and tenogenic differentiation of tendon stem/progenitor cell (TSPC). In vivo, CTHRC1 deletion impairs tendon healing, while its overexpression reverses the detrimental effects caused by CTHRC1 deficiency. Mechanistically, proteomics on TSPC stimulated with recombinant CTHRC1 reveal that CTHRC1 activates the mitogen-activated protein kinase (MAPK) signaling pathway via binding to epidermal growth factor receptor (EGFR), which in turn promotes the proliferative, migrative, and tenogenic capacities of TSPC to attenuate Achilles tendinopathy. Conversely, inhibiting EGFR reverses the tendon-healing effect of CRHRC1. The study demonstrates that CTHRC1 can promote the proliferative, migrative, and tenogenic capacities of TSPC, ultimately facilitating tendon healing through activating the EGFR/MAPK signaling pathway. CTHRC1 holds promise as a potential intervention for tendinopathy.

WTAP promotes laryngeal carcinoma cell progression by posttranscriptional activation of CTHRC1 in an m6A-YTHDF1-dependent way.

Laryngeal carcinoma is one of the malignancies in the head and neck region with high incidence and mortality. Despite advances in therapeutic modalities, the 5-year survival rate remains low. Wilms tumor 1-associated protein (WTAP) has been reported to regulate cancer progression, however, its role and mechanism in regulating laryngeal carcinoma development remain unclear. In this study, the expressions of WTAP, collagen triple helix repeat containing 1 (CTHRC1), and YTH N6-methyladenosine RNA binding protein F1 (YTHDF1) and other molecules were detected by quantitative real-time polymerase chain reaction or western blotting. Cell viability and colony formation rate were determined by cell counting kit-8 assay and cell colony formation assay. Cell migration and invasion were investigated by transwell assay. The relationship between CTHRC1 and YTHDF1 was identified by RNA immunoprecipitation assay. The results showed that WTAP and CTHRC1 were upregulated in laryngeal carcinoma tissues and cells. WTAP or CTHRC1 silencing inhibited the proliferation, migration and invasion of laryngeal carcinoma cells. WTAP knockdown inhibited CTHRC1 mRNA stability by suppressing CTHRC1 m6A modification and YTHDF1 from recognizing CTHRC1 m6A sites. Moreover, CTHRC1 overexpression attenuated WTAP knockdown-mediated effects on laryngeal carcinoma cell phenotypes and the expression of β-catenin, C-myc and cyclinD1. Thus, WTAP facilitated CTHRC1 mRNA stability in an m6A-dependent manner to activate the Wnt/β-catenin pathway and promote laryngeal carcinoma cell malignant phenotypes.

CTHRC1 is associated with BRAF(V600E) mutation and correlates with prognosis, immune cell infiltration, and drug resistance in colon cancer, thyroid cancer, and melanoma.

Colon cancer, thyroid cancer, and melanoma are common malignant tumors that seriously threaten human health globally. The B-Raf proto-oncogene, serine/threonine kinase (BRAF)(V600E) mutation is an important driver gene mutation in these cancer types. In this study, we identified that collagen triple helix repeat containing 1 (CTHRC1) expression was associated with the BRAF(V600E) mutation in colon cancer, thyroid cancer, and melanoma. Based on database analysis and clinical tissue studies, CTHRC1 was verified to correlate with poor prognosis and worse clinicopathological features in colon cancer and thyroid cancer patients, but not in patients with melanoma. Several signaling pathways, immune cell infiltration, and immunotherapy markers were associated with CTHRC1 expression. Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma.

CTHRC1 serves as an indicator in biliary atresia for evaluating the stage of liver fibrosis and predicting prognosis

BackgroundLiver fibrosis is a pathological feature of biliary atresia (BA). However, both histological fibrosis stage and existing biomarkers fail to predict prognosis at the time of hepatoportonterostomy (HPE). AimsTo explore the role of collagen triple- helix repeat containing-1 (CTHRC1) in BA. MethodsCTHRC1 expression levels were detected and its association with liver fibrosis stage was analyzed in patients with BA. Immunohistochemistry and immunofluorescent analyses were performed to detect the expression and localization of CTHRC1. Epithelial-mesenchymal transition (EMT) and proliferation were analyzed in cholangiocytes treated with recombinant human CTHRC1 protein. Survival analyses were performed to assess the prognostic value of CTHRC1 in patients with BA. ResultsCTHRC1 was upregulated in BA, and its expression level was positively correlated with fibrosis-related markers and the severity of liver fibrosis. In liver tissue CTHRC1 was co-localized with CK19 and highly expressed in patients with severe liver fibrosis. Further experiments revealed that CTHRC1 promoted cholangiocyte EMT and proliferation. Additionally, CTHRC1 expression levels at HPE could predict the 2-year native liver survival (NLS). ConclusionsCTHRC1 promotes the EMT and proliferation of cholangiocytes and indicate the stage of liver fibrosis. The CTHRC1 expression levels can predict outcomes of BA.

CTHRC1 is a prognostic biomarker correlated with immune infiltration in head and neck squamous cell carcinoma

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, characterized by high morbidity, high mortality, and poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) has been shown to be highly expressed in various cancers. However, its biological functions, potential role as a biomarker, and its relationship with immune infiltrates in HNSCC remain unclear. Our principal objective was to analyze CTHRC1 expression, its prognostic implications, biological functions, and its effects on the immune system in HNSCC patients using bioinformatics analysis.MethodsThe expression matrix was obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). CTHRC1 expression in HNSCC was analyzed between tumor and adjacent normal tissues, different stages were compared, and its impact on clinical prognosis was assessed using Kaplan-Meier analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Variation Analysis (GSVA) were employed for enrichment analysis. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to analyze protein-protein interactions. Pearson correlation tests were used to investigate the association between CTHRC1 expression and immune checkpoints. The correlation between CTHRC1 and immune infiltration was investigated using CIBERSORT, TIMER, and ESTIMATE.ResultsCompared to adjacent normal tissues, CTHRC1 was found to be highly overexpressed in tumors. Increased expression of CTHRC1 was more evident in the advanced stage of HNSCC and predicted a poor prognosis. Most genes related to CTHRC1 in HNSCC were enriched in physiological functions of Extracellular matrix(ECM) and tumor. Furthermore, several immune checkpoints, such as TNFSF4 and CD276 have been shown to be associated with CTHRC1 expression. Notably, the level of CTHRC1 expression correlated significantly with immune infiltration levels, particularly activated macrophages in HNSCC.ConclusionsHigh expression of CTHRC1 predicts poor prognosis and is associated with immune infiltration in HNSCC, confirming its utility as a tumor marker for HNSCC.Trial registrationNot applicable. All data are from public databases and do not contain any clinical trials.

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis.

Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.

Enter the Matrix: Fibroblast-immune interactions shape ECM deposition in health and disease.

Fibroblasts, non-hematopoietic cells of mesenchymal origin, are tissue architects which regulate the topography of tissues, dictate tissue resident cell types, and drive fibrotic disease. Fibroblasts regulate the composition of the extracellular matrix (ECM), a 3-dimensional network of macromolecules that comprise the acellular milieu of tissues. Fibroblasts can directly and indirectly regulate immune responses by secreting ECM and ECM-bound molecules to shape tissue structure and influence organ function. In this review, we will highlight recent studies which elucidate the mechanisms by which fibroblast-derived ECM factors (e.g., collagens, fibrillar proteins) regulate ECM architecture and subsequent immune responses, with a focus on macrophages. As examples of fibroblast-derived ECM proteins, we examine Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Transforming Growth Factor-β-inducible protein (TGFBI), also known as BIGH3. We address the need for investigation into how diverse fibroblast populations coordinate immune responses by modulating ECM, including the fibroblast-ECM-immune axis and the precise molecular mediators and pathways which regulate these processes. Finally, we will outline how novel research identifying key regulators of ECM deposition is critical for therapeutic development for fibrotic diseases and cancer.

Expression, Prognostic Value, and Biological Function of CTHRC1 in Different Types of Gliomas: A Bioinformatic Analysis and Experiment Validation.

In recent years, abnormal expression of collagen triple helix repeat containing 1 (CTHRC1) has been found in some tumors, closely related to the poor prognosis of cancer patients. However, the clinical significance of CTHRC1 in gliomas is not completely understood. We investigated the expression, prognostic value, and potential biological function of CTHRC1 in different types of gliomas through bioinformatics analysis and experimental verification. Bioinformatics analysis revealed several key findings regarding the expression and clinical significance of CTHRC1 in gliomas. First, the analysis demonstrated a positive correlation between CTHRC1 expression and the World Health Organization (WHO) grading of gliomas, a relationship that was validated through immunohistochemistry experiments. In addition, a trend was observed in which CTHRC1 expression increased with the extent of glioma invasion, as supported by Western blot experiments. Subsequent bioinformatics analysis identified the mesenchymal subtype of gliomas as having the highest levels of CTHRC1 expression, a finding reinforced by immunohistochemical staining. Moreover, high CTHRC1 expression was associated with poor prognosis in gliomas and emerged as an independent prognostic factor, with varying impacts on prognosis between low-grade gliomas (LGGs) and glioblastoma (GBM) subgroups. Notably, comparative analysis unveiled distinct patterns of immune infiltration of CTHRC1 in LGG and GBM. Furthermore, alterations in copy number variations and DNA methylation were identified as potential mechanisms underlying elevated CTHRC1 levels in gliomas. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that CTHRC1 and its associated genes mainly function in the extracellular matrix and participate in tumor-related signaling pathways. The CTHRC1 has shown significant clinical utility as a prognostic marker and mesenchymal subtype marker of glioma.

CTHRC1 promotes colorectal cancer progression by recruiting tumor-associated macrophages via up-regulation of CCL15.

Tumor-associated macrophages (TAMs) represent a key factor in the tumor immune microenvironment (TME), exerting significant influence over tumor migration, invasion, immunosuppressive features, and drug resistance. Collagen triple helix repeat containing 1 (CTHRC1), a 30 KDa protein which was secreted during the tissue-repair process, is highly expressed in several malignant tumors, including colorectal cancer (CRC). Previous studies demonstrated that CTHRC1 expression in TAMs was positively correlated to M2 macrophage polarization and liver metastasis, while our discovery suggesting a novel mechanism that CTHRC1 secreted from cancer cell could indirectly interplay with TAMs. In this study, the high expression level of CTHRC1 was evaluated in CRC based on GEO and TCGA databases. Further, CTHRC1 was detected high in all stages of CRC patients by ELISA and was correlated to poor prognosis. Multispectral imaging of IHC demonstrated that M2 macrophage infiltration was increased accompanied with CTHRC1 enrichment, suggesting that CTHRC1 may have chemotactic effect on macrophages. In vitro, CTHRC1 could have chemotactic ability of macrophage in the presence of HT-29 cell line. Cytokine microarray revealed that CTHRC1 could up-regulate the CCL15 level of HT-29, pathway analysis demonstrated that CTHRC1 could regulate CCL15 by controlling the TGFβ activation and Smad phosphorylation level. In vivo, knocking down of CTHRC1 from CT-26 also inhibits tumor formation. In conclusion, CTHRC1 could promote the chemotactic ability of macrophages by up-regulating CCL15 via TGFβ/Smad pathway; additionally, a high level of CTHRC1 could promote macrophage's M2 polarization. This discovery may be related to tumor immune tolerance and tumor immunotherapy resistance in CRC. KEY MESSAGES: CTHRC1 promotes CRC progression by up-regulating CCL15 via TGF-β/Smad pathways to further recruit tumor-associated macrophages. By the means of autocrine or paracrine, CTHRC1 can indeed promote macrophage chemotaxis and enhance the infiltration of macrophages in tumor tissues but in the presence of tumor cells. CAFs were another source of CTHRC1, indicating CTHRC1 can infiltrate tumor islet as well as the stomal and be secreted from both tumor cells and CAFs. This study validated CTHRC1 as a potential immune therapy target CRC.

Role of serum Collagen triple helix repeat containing 1(CTHRC1) protein in Rheumatoid arthritis and its relation to disease activity

Role of serum Collagen triple helix repeat containing 1(CTHRC1) protein in Rheumatoid arthritis and its relation to disease activity

The Role of Collagen Triple-Helix Repeat-Containing 1 (CTHRC1) as a Diagnostic Biomarker for Rheumatoid Arthritis

Background Many patients are seronegative for anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), and there is a need for novel serological biomarkers to help close this serological gap and improve early diagnosis. The purpose of this study was to determine whether plasma levels of the collagen triple helix repeat containing 1 (CTHRC1) protein can serve as a blood-based biomarker for improved diagnosis of rheumatoid arthritis (RA) patients. Objective Evaluate the levels of the collagen triple helix repeat containing-1 (CTHRC1) protein in RA patients' serum in order to detect its role as a diagnostic biomarker in Rheumatoid Arthritis patients & determine its value in assessment of disease activity in Rheumatoid Arthritis patients. Methods This study included twenty five adult patients with clinical evidence of rheumatoid arthritis and twenty five healthy matched age and sex as control subjects. All underwent history taking, clinical examination, assessment of disease activity with modified Disease Activity 28 (DAS28), Laboratory investigations including Complete blood count (CBC), erythrocytes sedimentation rate (ESR), C-Reactive Protein (CRP), Liver function tests, Kidney function tests, qualitative assessment of RF, anti CCP Ab and CTHRC1 serum levels. Special attention had been given to patients (nine out of twenty five patients) diagnosed in early disease process (1-2 months). Results Serum levels of CTHRC1 were significantly higher in patients than control group (p > 0,001) with sensitivity of 100% and specificity of 88%. It showed significant positive correlation with Anti-CCP (r = 0.498) (p < 0.011) and with RF (t= -6.489) (p <<0.001) as diagnostic markers for RA. Serum levels of CTHRC1 showed statistically significant difference between patients in early, late disease process and controls. Conclusion serum CTHRC1 level was higher in RA patients which serve as a diagnostic marker for RA with statistically significant correlation with early disease process highlighting its role as a diagnostic marker for RA.

Integrated analysis of single cell and bulk RNA sequencing identifies CTHRC1+ INHBA+ CAF as drivers of colorectal cancer progression.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and a critical factor in the progression of colorectal cancer (CRC). The aim of this study was to screen for CAFs specific genes that could serve as promising therapeutic targets for CRC patients. Our findings showed a significant increase in the proportion of fibroblasts in CRC tissues, and a high proportion of fibroblasts was associated with immune escape and poor prognosis in CRC. Collagen triple helix repeat containing 1 (CTHRC1) and inhibin subunit beta A (INHBA) were identified as key genes in the progression of CRC, primarily expressed in CAFs and significantly upregulated in CRC tissues. We defined CTHRC1 and INHBA as cancer-associated fibroblast-related genes (CAFRGs), which were associated with poor prognosis in CRC and macrophage polarization. CAFRGs promoted immune escape and metastasis in CRC and were good predictors of immune therapy response. Drug sensitivity analysis showed that the high expression group of CAFRGs was sensitive to 15 chemotherapy drugs, while the low expression group was sensitive to only 3. Clustering of fibroblasts in the tumor revealed that CTHRC1+ INHBA+ CAF was a poor prognostic factor in CRC and was associated with extracellular matrix remodeling and immune regulation. In conclusion, our study provides new theoretical basis for effective treatment strategies and therapeutic targets for CRC.

Predicting key gene related to immune infiltration and myofibroblast-like valve interstitial cells in patients with calcified aortic valve disease based on bioinformatics analysis.

Calcified aortic valve disease (CAVD) is the most prevalent valvular disease that can be treated only through valve replacement. We aimed to explore potential biomarkers and the role of immune cell infiltration in CAVD progression through bioinformatics analysis. Differentially ex-pressed genes (DEGs) were screened out based on three microarray datasets: GSE12644, GSE51472 and GSE83453. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to evaluate gene expression differences. Machine learning algorithms and DEGs were used to screen key gene. We used CIBERSORT to evaluate the immune cell infiltration of CAVD and evaluated the correlation between the biomarkers and infiltrating immune cells. We also compared bioinformatics analysis results with the valve interstitial cells (VICs) gene expression in single-cell RNA sequencing. Collagen triple helix repeat containing 1 (CTHRC1) was identified as the key gene of CAVD. We identified a cell subtype valve interstitial cells-fibroblast, which was closely associated with fibro-calcific progress of aortic valve. CTHRC1 highly expressed in the VIC subpopulation. Immune infiltration analysis demonstrated that mast cells, B cells, dendritic cells and eosinophils were involved in pathogenesis of CAVD. Correlation analysis demonstrated that CTHRC1 was correlated with mast cells mostly. In summary, the study suggested that CTHRC1 was a key gene of CAVD and CTHRC1 might participate in the potential molecular pathways involved in the connection between infiltrating immune cells and myofibroblast phenotype VICs.

CTHRC1 Induces Pancreatic Stellate Cells (PSCs) into Myofibroblast-like Cancer-Associated Fibroblasts (myCAFs).

[BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1-PSCs-cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation.

Estimation levels of CTHRC1and some cytokines in Iraqi patients with Rheumatoid Arthritis

Collagen triple helix repeat containing-1 (CTHRC1) is an essential marker for Rheumatoid Arthritis (RA), but its relationship with pro-inflammatory, anti-inflammatory, and inflammatory markers has been scantily covered in extant literature. To evaluate the level of CTHRC1 protein in the sera of 100 RA patients and 25 control and compare levels of tumour necrosis factor alpha (TNF-α), interleukin 10 (IL-10), RA disease activity (DAS28), and inflammatory factors. Higher significant serum levels of CTHRC1 (29.367 ng/ml), TNF-α (63.488 pg/ml), and IL-10 (67.1 pg/ml) were found in patient sera as compared to that in control sera (CTHRC1 = 15.732 ng/ml, TNF-α = 33.788 pg/ml, and IL-10 = 25.122 pg/ml). There was no significant correlation between the level of serum CTHRC1 and DAS28 (r = 0.046, P = 0.650), while there were positive significant correlations between the levels of serum CTHRC1 and CRP (r = 0.372, P = 0.0001), ACPA (r = 0.254, P = 0.01), TNF-α (r = 0.202, P = 0.044), and IL-10 (r = 0.260, P = 0.0001). The level of CTHRC1 (> 25.385 ng/ml) in combination with the levels of CRP and ACPA provided a good indication of RA prediction with sensitivity = 71.0%, specificity = 100.0%, accuracy = 0.71%, positive predictive value (PPV) = 100.0%, and negative predictive value (NPV) = 46.3%. The study showed a significant correlation between the levels of CTHRC1 and TNF-α, and IL-10. These molecules may play a prominent role in the diagnostic and etiology of RA

Potential value of collagen triple helix repeat containing-1 (CTHRC1) in systemic lupus erythematosus (SLE) patients with arthritis detected clinically or by musculoskeletal ultrasound

Potential value of collagen triple helix repeat containing-1 (CTHRC1) in systemic lupus erythematosus (SLE) patients with arthritis detected clinically or by musculoskeletal ultrasound

CTHRC1 promotes anaplastic thyroid cancer progression by upregulating the proliferation, migration, and invasion of tumor cells.

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive tumor with a high mortality rate and poor prognosis. However, the pathogenesis of ATC is complex and poorly understood, and the effective treatment options are limited. Analysis of data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases showed that collagen triple helix repeat containing-1 (CTHRC1) was specifically upregulated in ATC tissues and was negatively correlated with overall survival (OS) in thyroid carcinoma patients. In vitro knockdown of CTHRC1 dramatically decreased the proliferation, migration, and invasion abilities of ATC cells, and in vivo studies in BALB/c nude mice confirmed that CTHRC1 knockdown significantly inhibited tumor growth. Mechanistically, CTHRC1 knockdown was found to suppress the Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT) at the protein level. These findings suggest that CTHRC1 promotes the progression of ATC via upregulating tumor cell proliferation, migration, and invasion, which may be achieved by activating the Wnt/β-catenin pathway and EMT.

CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review).

Collagen triple helix repeat containing 1 (CTHRC1) is a gene discovered in 2005; it is highly conserved, and no homologous proteins have been disclosed thus far. A number of studies have shown that CTHRC1 is present in normal tissues and organs, and it has vital functions in physiological processes, including participating in the regulation of metabolism, arterial remodeling, bone formation and myelination of the peripheral nervous system. It has been reported that abnormal expression of CTHRC1 is involved in the carcinogenesis of various human organs, such as the breast, colon, pancreas, lung, stomach and liver. Therefore, the present review aims to collate all known findings and results on the regulation of CTHRC1 expression and related signaling pathways. To conclude, this review also provides a hypothesis of the functional mechanism of this gene.

Elevated Levels of Plasma Collagen Triple Helix Repeat Containing 1 (CTHRC1) Are Strongly Associated with eGFR and Albuminuria in Chronic Kidney Disease.

Background: Chronic kidney disease (CKD) has various etiologies, making it impossible to fully understand its complex pathophysiology. Elevated levels of plasma creatinine, proteinuria, and albuminuria and declined eGFR are traits observed in CKD patients. The current study attempts to highlight the collagen triple helix repeat containing 1 (CTHRC1) protein as a putative blood biomarker for CKD in addition to existing recognized indicators of CKD progression. Methods: A total of 26 CKD patients and 18 healthy controls were enrolled in this study. Clinical characteristics and complete blood and biochemical analyses were collected, and human ELISA kits were used to detect possible CKD biomarkers. Results: The study's findings showed that CTHRC1 correlates with key clinical markers of kidney function such as 24 h urine total protein, creatinine, urea, and uric acid. In addition, CTHRC1 demonstrated a strong significant difference (p ≤ 0.0001) between the CKD and control group. Conclusions: Our research demonstrates that the plasma level of CTHRC1 can distinguish between those with CKD and healthy patients. Plasma CTHRC1 levels may aid in the diagnosis of CKD given the current state of knowledge, and these results call for further investigation in a wider, more diverse patient group.

Long non-coding RNA H19 regulates matrisome signature and impacts cell behavior on MSC-engineered extracellular matrices

BackgroundThe vast and promising class of long non-coding RNAs (lncRNAs) has been under investigation for distinct therapeutic applications. Nevertheless, their role as molecular drivers of bone regeneration remains poorly studied. The lncRNA H19 mediates osteogenic differentiation of Mesenchymal Stem/Stromal Cells (MSCs) through the control of intracellular pathways. However, the effect of H19 on the extracellular matrix (ECM) components is still largely unknown. This research study was designed to decode the H19-mediated ECM regulatory network, and to reveal how the decellularized siH19-engineered matrices influence MSC proliferation and fate. This is particularly relevant for diseases in which the ECM regulation and remodeling processes are disrupted, such as osteoporosis.MethodsMass spectrometry-based quantitative proteomics analysis was used to identify ECM components, after oligonucleotides delivery to osteoporosis-derived hMSCs. Moreover, qRT-PCR, immunofluorescence and proliferation, differentiation and apoptosis assays were performed. Engineered matrices were decellularized, characterized by atomic force microscopy and repopulated with hMSC and pre-adipocytes. Clinical bone samples were characterized by histomorphometry analysis.ResultsOur study provides an in-depth proteome-wide and matrisome-specific analysis of the ECM proteins controlled by the lncRNA H19. Using bone marrow-isolated MSC from patients with osteoporosis, we identified fibrillin-1 (FBN1), vitronectin (VTN) and collagen triple helix repeat containing 1 (CTHRC1), among others, as having different pattern levels following H19 silencing. Decellularized siH19-engineered matrices are less dense and have a decreased collagen content compared with control matrices. Repopulation with naïve MSCs promotes a shift towards the adipogenic lineage in detriment of the osteogenic lineage and inhibits proliferation. In pre-adipocytes, these siH19-matrices enhance lipid droplets formation. Mechanistically, H19 is targeted by miR-29c, whose expression is decreased in osteoporotic bone clinical samples. Accordingly, miR-29c impacts MSC proliferation and collagen production, but does not influence ALP staining or mineralization, revealing that H19 silencing and miR-29c mimics have complementary but not overlapping functions.ConclusionOur data suggest H19 as a therapeutic target to engineer the bone ECM and to control cell behavior.